char = V;code = 86
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = G;code = 71
char = 1;code = 49
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = S;code = 83
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = L;code = 76
char = N;code = 78
char = C;code = 67
char = a;code = 97
char = P;code = 80
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = K;code = 75
char = i;code = 105
char = p;code = 112
char = 1;code = 49
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = k;code = 107
char = 2;code = 50
char = ;code = 32
char = m;code = 109
char = i;code = 105
char = s;code = 115
char = l;code = 108
char = o;code = 111
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = z;code = 122
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = m;code = 109
char = .;code = 46
result sql = Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm.
Vitamin D inhibits G1 to S progression in LNCaP prostate cancer cells through p27Kip1 stabilization and Cdk2 mislocalization to the cytoplasm.
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = 3;code = 51
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = );code = 41
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = e;code = 101
char = r;code = 114
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = u;code = 117
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = v;code = 118
char = i;code = 105
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = u;code = 117
char = m;code = 109
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = L;code = 76
char = N;code = 78
char = -;code = 45
char = C;code = 67
char = a;code = 97
char = P;code = 80
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = K;code = 75
char = i;code = 105
char = p;code = 112
char = 1;code = 49
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = h;code = 104
char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = d;code = 100
char = k;code = 107
char = 2;code = 50
char = );code = 41
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = b;code = 98
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = G;code = 71
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = v;code = 118
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = 3;code = 51
char = .;code = 46
char = 5;code = 53
char = -;code = 45
char = k;code = 107
char = b;code = 98
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = a;code = 97
char = g;code = 103
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = l;code = 108
char = u;code = 117
char = c;code = 99
char = i;code = 105
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = d;code = 100
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 5;code = 53
char = ';code = 39
char = -;code = 45
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 3;code = 51
char = ';code = 39
char = -;code = 45
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
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char = a;code = 97
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char = r;code = 114
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char = g;code = 103
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char = n;code = 110
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = 2;code = 50
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char = a;code = 97
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char = r;code = 114
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char = g;code = 103
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
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char = i;code = 105
char = n;code = 110
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char = s;code = 115
char = y;code = 121
char = n;code = 110
char = t;code = 116
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char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = u;code = 117
char = l;code = 108
char = s;code = 115
char = e;code = 101
char = -;code = 45
char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 3;code = 51
char = 5;code = 53
char = S;code = 83
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char = l;code = 108
char = a;code = 97
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = d;code = 100
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char = 7;code = 55
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char = r;code = 114
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char = v;code = 118
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
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char = a;code = 97
char = s;code = 115
char = e;code = 101
char = d;code = 100
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char = 7;code = 55
char = ;code = 32
char = p;code = 112
char = r;code = 114
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char = h;code = 104
char = a;code = 97
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char = f;code = 102
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char = l;code = 108
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char = f;code = 102
char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 1;code = 49
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char = 2;code = 50
char = 5;code = 53
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char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
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char = .;code = 46
char = ;code = 32
char = B;code = 66
char = e;code = 101
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = k;code = 107
char = 2;code = 50
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = r;code = 114
char = 1;code = 49
char = 8;code = 56
char = 7;code = 55
char = ;code = 32
char = t;code = 116
char = a;code = 97
char = r;code = 114
char = g;code = 103
char = e;code = 101
char = t;code = 116
char = s;code = 115
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char = p;code = 112
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = S;code = 83
char = k;code = 107
char = p;code = 112
char = 2;code = 50
char = -;code = 45
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = a;code = 97
char = d;code = 100
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
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char = e;code = 101
char = x;code = 120
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char = m;code = 109
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char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = h;code = 104
char = o;code = 111
char = s;code = 115
char = p;code = 112
char = h;code = 104
char = o;code = 111
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char = y;code = 121
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = 2;code = 50
char = 7;code = 55
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char = i;code = 105
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char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = -;code = 45
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = d;code = 100
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char = c;code = 99
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char = l;code = 108
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char = .;code = 46
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
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char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
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char = d;code = 100
char = e;code = 101
char = c;code = 99
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char = e;code = 101
char = a;code = 97
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char = e;code = 101
char = l;code = 108
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = r;code = 114
char = 1;code = 49
char = 8;code = 56
char = 7;code = 55
char = ;code = 32
char = p;code = 112
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char = o;code = 111
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char = p;code = 112
char = h;code = 104
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char = a;code = 97
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char = e;code = 101
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char = p;code = 112
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char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = r;code = 114
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char = 8;code = 56
char = 7;code = 55
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char = d;code = 100
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char = a;code = 97
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char = a;code = 97
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char = i;code = 105
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char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
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char = a;code = 97
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char = d;code = 100
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char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
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char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
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char = r;code = 114
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char = d;code = 100
char = u;code = 117
char = c;code = 99
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char = ;code = 32
char = S;code = 83
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char = 2;code = 50
char = ;code = 32
char = p;code = 112
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char = t;code = 116
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char = e;code = 101
char = l;code = 108
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = L;code = 76
char = N;code = 78
char = C;code = 67
char = a;code = 97
char = P;code = 80
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
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char = a;code = 97
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char = e;code = 101
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char = s;code = 115
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char = b;code = 98
char = y;code = 121
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char = d;code = 100
char = k;code = 107
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char = a;code = 97
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char = a;code = 97
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char = a;code = 97
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char = e;code = 101
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char = r;code = 114
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = r;code = 114
char = 1;code = 49
char = 6;code = 54
char = 0;code = 48
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char = p;code = 112
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char = o;code = 111
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char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = b;code = 98
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char = c;code = 99
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char = o;code = 111
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char = a;code = 97
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char = a;code = 97
char = s;code = 115
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char = a;code = 97
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char = T;code = 84
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char = 4;code = 52
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char = .;code = 46
char = ;code = 32
char = I;code = 73
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char = ,;code = 44
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char = O;code = 79
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char = 2;code = 50
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char = 3;code = 51
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char = d;code = 100
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char = C;code = 67
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char = a;code = 97
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char = f;code = 102
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char = c;code = 99
char = o;code = 111
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char = y;code = 121
char = .;code = 46
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char = I;code = 73
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = o;code = 111
char = n;code = 110
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = d;code = 100
char = k;code = 107
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char = b;code = 98
char = y;code = 121
char = ;code = 32
char = 1;code = 49
char = ,;code = 44
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char = 5;code = 53
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char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
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char = m;code = 109
char = a;code = 97
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char = t;code = 116
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char = u;code = 117
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char = w;code = 119
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char = s;code = 115
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char = r;code = 114
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result sql = 1,25-(OH)2 vitamin D3 (1,25-(OH)2D3) exerts antiproliferative effects via cell cycle regulation in a variety of tumor cells, including prostate. We have previously shown that in the human prostate cancer cell line LN-CaP, 1,25-(OH)2D3 mediates an increase in cyclin-dependent kinase inhibitor p27Kip1 levels, inhibition of cyclin-dependent kinase 2 (Cdk2) activity, hypophosphorylation of retinoblastoma protein, and accumulation of cells in G1. In this study, we investigated the mechanism whereby 1,25-(OH)2D3 increases p27 levels. 1,25-(OH)2D3 had no effect on p27 mRNA levels or on the regulation of a 3.5-kb fragment of the p27 promoter. The rate of p27 protein synthesis was not affected by 1,25-(OH)2D3 as measured by luciferase activity driven by the 5'- and 3'-untranslated regions of p27 that regulate p27 protein synthesis. Pulse-chase analysis of 35S-labeled p27 revealed an increased p27 protein half-life with 1,25-(OH)2D3 treatment. Because Cdk2-mediated phosphorylation of p27 at Thr187 targets p27 for Skp2-mediated degradation, we examined the phosphorylation status of p27 in 1,25-(OH)2D3-treated cells. 1,25-(OH)2D3 decreased levels of Thr187 phosphorylated p27, consistent with inhibition of Thr187 phosphorylation-dependent p27 degradation. In addition, 1,25-(OH)2D3 reduced Skp2 protein levels in LNCaP cells. Cdk2 is activated in the nucleus by Cdk-activating kinase through Thr160 phosphorylation and by cdc25A phosphatase via Thr14 and Tyr15 dephosphorylation. Interestingly, 1,25-(OH)2D3 decreased nuclear Cdk2 levels as assessed by subcellular fractionation and confocal microscopy. Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. These data suggest that Cdk2 mislocalization is central to the antiproliferative effects of 1,25-(OH)2D3.

Publication: J. Biol. Chem. 2003 Nov 21 ;278(47)::46862-8.
Publication Date: 2003 Nov 21
Study Author(s): Yang, Eddy S;Burnstein, Kerry L;
Institution: Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, FL 33136, USA.
Shortcut link to this study:
1,25-(OH)2 vitamin D3 (1,25-(OH)2D3) exerts antiproliferative effects via cell cycle regulation in a variety of tumor cells, including prostate. We have previously shown that in the human prostate cancer cell line LN-CaP, 1,25-(OH)2D3 mediates an increase in cyclin-dependent kinase inhibitor p27Kip1 levels, inhibition of cyclin-dependent kinase 2 (Cdk2) activity, hypophosphorylation of retinoblastoma protein, and accumulation of cells in G1. In this study, we investigated the mechanism whereby 1,25-(OH)2D3 increases p27 levels. 1,25-(OH)2D3 had no effect on p27 mRNA levels or on the regulation of a 3.5-kb fragment of the p27 promoter. The rate of p27 protein synthesis was not affected by 1,25-(OH)2D3 as measured by luciferase activity driven by the 5'- and 3'-untranslated regions of p27 that regulate p27 protein synthesis. Pulse-chase analysis of 35S-labeled p27 revealed an increased p27 protein half-life with 1,25-(OH)2D3 treatment. Because Cdk2-mediated phosphorylation of p27 at Thr187 targets p27 for Skp2-mediated degradation, we examined the phosphorylation status of p27 in 1,25-(OH)2D3-treated cells. 1,25-(OH)2D3 decreased levels of Thr187 phosphorylated p27, consistent with inhibition of Thr187 phosphorylation-dependent p27 degradation. In addition, 1,25-(OH)2D3 reduced Skp2 protein levels in LNCaP cells. Cdk2 is activated in the nucleus by Cdk-activating kinase through Thr160 phosphorylation and by cdc25A phosphatase via Thr14 and Tyr15 dephosphorylation. Interestingly, 1,25-(OH)2D3 decreased nuclear Cdk2 levels as assessed by subcellular fractionation and confocal microscopy. Inhibition of Cdk2 by 1,25-(OH)2D3 may thus involve two mechanisms: 1) reduced nuclear Cdk2 available for cyclin binding and activation and 2) impairment of cyclin E-Cdk2-dependent p27 degradation through cytoplasmic mislocalization of Cdk2. These data suggest that Cdk2 mislocalization is central to the antiproliferative effects of 1,25-(OH)2D3.
PMID: 12954644

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