|
|
char = I;code = 73
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = c;code = 99
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char = r;code = 114
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char = n;code = 110
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char = l;code = 108
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char = i;code = 105
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = C;code = 67
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char = K;code = 75
char = 6;code = 54
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char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
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char = ;code = 32
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char = n;code = 110
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char = n;code = 110
char = ;code = 32
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char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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char = e;code = 101
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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
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = y;code = 121
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char = d;code = 100
char = i;code = 105
char = s;code = 115
char = r;code = 114
char = u;code = 117
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char = S;code = 83
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char = r;code = 114
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char = c;code = 99
char = r;code = 114
char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
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char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = m;code = 109
char = e;code = 101
char = n;code = 110
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 = C;code = 67
char = D;code = 68
char = K;code = 75
char = 6;code = 54
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
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
result sql = Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter.
Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter.char = I;code = 73
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = 3;code = 51
char = -;code = 45
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = l;code = 108
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = 3;code = 51
char = C;code = 67
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = u;code = 117
char = n;code = 110
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char = ;code = 32
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char = a;code = 97
char = t;code = 116
char = u;code = 117
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
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char = o;code = 111
char = c;code = 99
char = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = B;code = 66
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = s;code = 115
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char = c;code = 99
char = a;code = 97
char = ;code = 32
char = v;code = 118
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char = g;code = 103
char = e;code = 101
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char = a;code = 97
char = b;code = 98
char = l;code = 108
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char = ,;code = 44
char = ;code = 32
char = c;code = 99
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = G;code = 71
char = (;code = 40
char = 1;code = 49
char = );code = 41
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
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char = l;code = 108
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char = ;code = 32
char = a;code = 97
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char = o;code = 111
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char = ;code = 32
char = h;code = 104
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char = m;code = 109
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char = M;code = 77
char = C;code = 67
char = F;code = 70
char = -;code = 45
char = 7;code = 55
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char = b;code = 98
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char = e;code = 101
char = a;code = 97
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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 = 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
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char = a;code = 97
char = t;code = 116
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char = i;code = 105
char = s;code = 115
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char = a;code = 97
char = c;code = 99
char = c;code = 99
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char = s;code = 115
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char = l;code = 108
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char = e;code = 101
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char = i;code = 105
char = n;code = 110
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char = o;code = 111
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char = ;code = 32
char = c;code = 99
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char = c;code = 99
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char = C;code = 67
char = D;code = 68
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char = m;code = 109
char = R;code = 82
char = N;code = 78
char = A;code = 65
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char = y;code = 121
char = ;code = 32
char = r;code = 114
char = a;code = 97
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char = ;code = 32
char = r;code = 114
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char = I;code = 73
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char = ;code = 32
char = W;code = 87
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = f;code = 102
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char = r;code = 114
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = d;code = 100
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result sql = Indole-3-carbinol (I3C), a compound naturally occurring in Brassica vegetables, can induce a G(1) cell cycle arrest of human MCF-7 breast cancer cells that is accompanied by the selective inhibition of cyclin-dependent kinase 6 (CDK6) expression. Reverse transcriptase-polymerase chain reaction analysis of CDK6 mRNA decay rates revealed that I3C had no effect on CDK6 transcript stability. We report the first identification and functional characterization of the CDK6 promoter in order to determine whether I3C inhibits CDK6 transcription. In MCF-7 cells stably transfected with CDK6 promoter-linked luciferase reporter plasmids, I3C inhibited CDK6 promoter activity in an I3C-specific response that was not a consequence of the growth-arrested state of the cells. Deletion analysis revealed a 167-base pair I3C-responsive region of the CDK6 promoter between -805 and -638. Site-specific mutations within this region revealed that both Sp1 and Ets-like sites, which are spaced 5 base pairs apart, were necessary for I3C responsiveness in the context of the CDK6 promoter. Electrophoretic mobility shift analysis of protein-DNA complexes formed with nuclear proteins isolated from I3C-treated and -untreated cells, in combination with supershift assays using Sp1 antibodies, demonstrated that the Sp1-binding site in the CDK6 promoter forms a specific I3C-responsive DNA-protein complex that contains the Sp1 transcription factor. Taken together, our results suggest that I3C down-regulates CDK6 transcription by targeting Sp1 at a composite DNA site in the CDK6 promoter.
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char = e;code = 101
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char = .;code = 46
result sql = Indole-3-carbinol inhibits CDK6 expression in human MCF-7 breast cancer cells by disrupting Sp1 transcription factor interactions with a composite element in the CDK6 gene promoter.
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result sql = Indole-3-carbinol (I3C), a compound naturally occurring in Brassica vegetables, can induce a G(1) cell cycle arrest of human MCF-7 breast cancer cells that is accompanied by the selective inhibition of cyclin-dependent kinase 6 (CDK6) expression. Reverse transcriptase-polymerase chain reaction analysis of CDK6 mRNA decay rates revealed that I3C had no effect on CDK6 transcript stability. We report the first identification and functional characterization of the CDK6 promoter in order to determine whether I3C inhibits CDK6 transcription. In MCF-7 cells stably transfected with CDK6 promoter-linked luciferase reporter plasmids, I3C inhibited CDK6 promoter activity in an I3C-specific response that was not a consequence of the growth-arrested state of the cells. Deletion analysis revealed a 167-base pair I3C-responsive region of the CDK6 promoter between -805 and -638. Site-specific mutations within this region revealed that both Sp1 and Ets-like sites, which are spaced 5 base pairs apart, were necessary for I3C responsiveness in the context of the CDK6 promoter. Electrophoretic mobility shift analysis of protein-DNA complexes formed with nuclear proteins isolated from I3C-treated and -untreated cells, in combination with supershift assays using Sp1 antibodies, demonstrated that the Sp1-binding site in the CDK6 promoter forms a specific I3C-responsive DNA-protein complex that contains the Sp1 transcription factor. Taken together, our results suggest that I3C down-regulates CDK6 transcription by targeting Sp1 at a composite DNA site in the CDK6 promoter.
Publication: J. Biol. Chem. 2001 Jun 22 ;276(25)::22332-40.
Publication Date: 2001 Jun 22
Study Author(s): Cram, E J;Liu, B D;Bjeldanes, L F;Firestone, G L;
Institution: Department of Molecular and Cell Biology, the Cancer Research Laboratory, University of California, Berkeley, California 94720, USA.
Shortcut link to this study:
Publication Date: 2001 Jun 22
Study Author(s): Cram, E J;Liu, B D;Bjeldanes, L F;Firestone, G L;
Institution: Department of Molecular and Cell Biology, the Cancer Research Laboratory, University of California, Berkeley, California 94720, USA.
Shortcut link to this study:
Indole-3-carbinol (I3C), a compound naturally occurring in Brassica vegetables, can induce a G(1) cell cycle arrest of human MCF-7 breast cancer cells that is accompanied by the selective inhibition of cyclin-dependent kinase 6 (CDK6) expression. Reverse transcriptase-polymerase chain reaction analysis of CDK6 mRNA decay rates revealed that I3C had no effect on CDK6 transcript stability. We report the first identification and functional characterization of the CDK6 promoter in order to determine whether I3C inhibits CDK6 transcription. In MCF-7 cells stably transfected with CDK6 promoter-linked luciferase reporter plasmids, I3C inhibited CDK6 promoter activity in an I3C-specific response that was not a consequence of the growth-arrested state of the cells. Deletion analysis revealed a 167-base pair I3C-responsive region of the CDK6 promoter between -805 and -638. Site-specific mutations within this region revealed that both Sp1 and Ets-like sites, which are spaced 5 base pairs apart, were necessary for I3C responsiveness in the context of the CDK6 promoter. Electrophoretic mobility shift analysis of protein-DNA complexes formed with nuclear proteins isolated from I3C-treated and -untreated cells, in combination with supershift assays using Sp1 antibodies, demonstrated that the Sp1-binding site in the CDK6 promoter forms a specific I3C-responsive DNA-protein complex that contains the Sp1 transcription factor. Taken together, our results suggest that I3C down-regulates CDK6 transcription by targeting Sp1 at a composite DNA site in the CDK6 promoter.
PMID: 11297539
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