char = P;code = 80
char = T;code = 84
char = P;code = 80
char = H;code = 72
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = o;code = 111
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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 = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = i;code = 105
char = r;code = 114
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = u;code = 117
char = a;code = 97
char = l;code = 108
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 = 46
result sql = PTPH1 cooperates with vitamin D receptor to stimulate breast cancer growth through their mutual stabilization.
PTPH1 cooperates with vitamin D receptor to stimulate breast cancer growth through their mutual stabilization.
char = T;code = 84
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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
char = ;code = 32
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = t;code = 116
char = l;code = 108
char = y;code = 121
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
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 = t;code = 116
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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 = s;code = 115
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = T;code = 84
char = K;code = 75
char = s;code = 115
char = );code = 41
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
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 = t;code = 116
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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 = a;code = 97
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = T;code = 84
char = P;code = 80
char = s;code = 115
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = m;code = 109
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 = 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 = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = g;code = 103
char = h;code = 104
char = ;code = 32
char = P;code = 80
char = T;code = 84
char = K;code = 75
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = -;code = 45
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = i;code = 105
char = s;code = 115
char = h;code = 104
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
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 = n;code = 110
char = g;code = 103
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ,;code = 44
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = u;code = 117
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 = P;code = 80
char = T;code = 84
char = P;code = 80
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = s;code = 115
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = k;code = 107
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = e;code = 101
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 = a;code = 97
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = T;code = 84
char = P;code = 80
char = H;code = 72
char = 1;code = 49
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
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 = 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 = n;code = 110
char = g;code = 103
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 = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = (;code = 40
char = V;code = 86
char = D;code = 68
char = R;code = 82
char = );code = 41
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
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 = 46
char = ;code = 32
char = P;code = 80
char = T;code = 84
char = P;code = 80
char = H;code = 72
char = 1;code = 49
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
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 = o;code = 111
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = 4;code = 52
char = 9;code = 57
char = %;code = 37
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = a;code = 97
char = n;code = 110
char = d;code = 100
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 = f;code = 102
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
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 = e;code = 101
char = x;code = 120
char = p;code = 112
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 = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = n;code = 110
char = c;code = 99
char = o;code = 111
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = i;code = 105
char = c;code = 99
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 = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = e;code = 101
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = P;code = 80
char = T;code = 84
char = P;code = 80
char = H;code = 72
char = 1;code = 49
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 = s;code = 115
char = ;code = 32
char = b;code = 98
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = t;code = 116
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 = g;code = 103
char = r;code = 114
char = o;code = 111
char = w;code = 119
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = a;code = 97
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 = i;code = 105
char = n;code = 110
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
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 = a;code = 97
char = t;code = 116
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 = 44
char = ;code = 32
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = ;code = 32
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 = o;code = 111
char = f;code = 102
char = ;code = 32
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = y;code = 121
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = u;code = 117
char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
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result sql = Tyrosine phosphorylation is tightly regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), and has a critical role in malignant transformation and progression. Although PTKs have a well-established role in regulating breast cancer growth, contribution of PTPs remains mostly unknown. Here, we report that the tyrosine phosphatase PTPH1 stimulates breast cancer growth through regulating vitamin D receptor (VDR) expression. PTPH1 was shown to be overexpressed in 49% of primary breast cancer and levels of its protein expression positively correlate with the clinic metastasis, suggesting its oncogenic activity. Indeed, PTPH1 promotes breast cancer growth by a mechanism independent of its phosphatase activity, but dependent of its stimulatory effect on the nuclear receptor VDR protein expression and depletion of induced VDR abolishes the PTPH1 oncogenic activity. Additional analyses showed that PTPH1 binds VDR and increases its cytoplasmic accumulation, leading to their mutual stabilization and stable expression of a nuclear localization-deficient VDR abolishes the growth-inhibitory activity of the receptor independent of 1,25-dihydroxyvitamin D3. These results reveal a new paradigm in which a PTP may stimulate breast cancer growth through increasing cytoplasmic translocation of a nuclear receptor, leading to their mutual stabilization.

Publication: Oncogene 2010 Nov 29 ;:.
Publication Date: 2010 Nov 29
Study Author(s): Zhi, H-Y;Hou, S-W;Li, R-S;Basir, Z;Xiang, Q;Szabo, A;Chen, G;
Institution: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, USA.
Shortcut link to this study:
Tyrosine phosphorylation is tightly regulated by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), and has a critical role in malignant transformation and progression. Although PTKs have a well-established role in regulating breast cancer growth, contribution of PTPs remains mostly unknown. Here, we report that the tyrosine phosphatase PTPH1 stimulates breast cancer growth through regulating vitamin D receptor (VDR) expression. PTPH1 was shown to be overexpressed in 49% of primary breast cancer and levels of its protein expression positively correlate with the clinic metastasis, suggesting its oncogenic activity. Indeed, PTPH1 promotes breast cancer growth by a mechanism independent of its phosphatase activity, but dependent of its stimulatory effect on the nuclear receptor VDR protein expression and depletion of induced VDR abolishes the PTPH1 oncogenic activity. Additional analyses showed that PTPH1 binds VDR and increases its cytoplasmic accumulation, leading to their mutual stabilization and stable expression of a nuclear localization-deficient VDR abolishes the growth-inhibitory activity of the receptor independent of 1,25-dihydroxyvitamin D3. These results reveal a new paradigm in which a PTP may stimulate breast cancer growth through increasing cytoplasmic translocation of a nuclear receptor, leading to their mutual stabilization.
PMID: 21119599

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