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

Oncogene volume 18, pages 6684–6691 (1999)Cite this article

Abstract

The BRCA-1 tumour supressor gene was identified on the basis of mutations which occur in familial breast cancer indicating that its inactivation can cause this disease. Although BRCA-1 does not appear to be mutated in sporadic breast cancer, its expression has been shown to be reduced in tumour material 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 family transcription factor at both the mRNA and protein levels. This elevated expression of Brn-3b is not found in normal mammary cells, benign tumours or 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 the related factor Brn-3a. Moreover, Brn-3b but not Brn-3a can strongly repress the BRCA-1 promoter approximately 20-fold in mammary tumour cells. To our knowledge, this is the first report of a transcription factor which regulates BRCA-1 expression. Thus, Brn-3b may play an important role in regulating expression of BRCA-1 in mammary tumours with enhanced expression of Brn-3b resulting in reduced BRCA-1 expression and thereby being potentially important in tumour development.

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Acknowledgements

We are most grateful to Dave Berry, Candis Tissue Bank Research Centre and Diane Barnes, Guys Hospital for tumour material. This work was supported by the Cancer Research Campaign and Wellbeing.

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Authors and Affiliations

  1. Department of Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, The Windeyer Building, 46 Cleveland Street, London, W1P 6DB, UK

    Vishwanie Budhram-Mahadeo, Daniel Ndisang & David S Latchman

  2. Department of Medicine, University of Pennsylvania Medical School, Philadelphia, 19104, Pennsylvania, PA, USA

    Theresa Ward & Barbara L Weber

  3. Department of Genetics, University of Pennsylvania Medical School, Philadelphia, PA 19104, Pennsylvania, USA

    Barbara L Weber

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  1. Vishwanie Budhram-Mahadeo
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Budhram-Mahadeo, V., Ndisang, D., Ward, T. et al. The Brn-3b POU family transcription factor represses expression of the BRCA-1 anti-oncogene in breast cancer cells. Oncogene 18, 6684–6691 (1999). https://doi.org/10.1038/sj.onc.1203072

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