Activation of CDK4 gene expression in human breast cancer cells by the Brn-3b POU family transcription factor.
The Brn-3b POU family transcription factor has previously been shown to be over-expressed in human breast cancer and to enhance the growth rate and anchorage independent growth of human breast cancer cells, acting at least in part by inhibiting the expression of the BRCA-1 anti-oncogene. Here we have used gene arrays to identify several other targets for Brn-3b in human breast cancer cells, including cyclin-dependent kinase 4 (CDK4). In particular, we show that levels of CDK4 mRNA and protein correlate with the levels of Brn-3b in breast cancer cell lines manipulated to express different levels of Brn-3b and in human breast cancer biopsies and that Brn-3b can activate the CDK4 promoter. The effect of Brn-3b on the growth regulatory CDK4 protein provides a further mechanism by which Brn-3b can regulate breast cancer cell growth and indicates that it can do this by activating as well as repressing specific target genes.
Samady
Laila
L
Medical Molecular Biology Unit, Institute of Child Health, University College London, London, UK.
Dennis
Jonathan
J
Budhram-Mahadeo
Vishwanie
V
Latchman
David S
DS
D001706:Biopsy; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C494190:POU4F2 protein, human; D011518:Proto-Oncogene Proteins; D050818:Transcription Factor Brn-3; D050820:Transcription Factor Brn-3B; D014157:Transcription Factors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases