The Brn-3b POU family transcription factor represses expression of the BRCA-1 anti-oncogene in breast cancer cells

The BRCA-1 tumour supressor gene was identified on the basis of mutations w hich occur in familial breast cancer indicating that its inactivation can c ause this disease. Although BRCA-1 does not appear to be mutated in sporadi c breast cancer, its expression has been shown to be reduced in tumour mate rial from such cases. We show here that mammary tumours which have reduced levels of BRCA-1 expression show enhanced expression of the Brn-3b POU fami ly transcription factor at both the mRNA and protein levels. This elevated expression of Brn-3b is not found in normal mammary cells, benign tumours o r in malignant tumour samples which do not exhibit reduced levels of BRCA-1 . In contrast, no correlation was noted between BRCA-1 and expression of th e related factor Brn-3a. Moreover, Brn-3b but not Brn-3a can strongly repre ss the BRCA-1 promoter approximately 20-fold in mammary tumour cells. To ou r knowledge, this is the first report of a transcription factor which regul ates BRCA-1 expression. Thus, Brn-3b may play an important role in regulati ng expression of BRCA-1 in mammary tumours with enhanced expression of Brn- 3b resulting in reduced BRCA-1 expression and thereby being potentially imp ortant in tumour development.