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Brca1 regulates in vitro differentiation of mammary epithelial cells

Abstract

Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.

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Acknowledgements

The authors wish to thank O Aprelikova and ET Liu, W Doppler, and DA Bochar and R Shiekhattar for the generous gift of cell lines and reagents, C Schneeberger for help with RT–PCR, E Hengstschläger-Ottnad for helpful discussion and for critically reading the manuscript. M Kubista was supported by the Austrian Ludwig Boltzmann Institute for Clinical and Experimental Oncology. This project was partially supported by the ‘Medizinisch-Wissenschaftlicher Fonds des Bürgermeisters des Bundeshauptstadt Wien’.

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Correspondence to Gerhard Bernaschek.

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Kubista, M., Rosner, M., Kubista, E. et al. Brca1 regulates in vitro differentiation of mammary epithelial cells. Oncogene 21, 4747–4756 (2002). https://doi.org/10.1038/sj.onc.1205580

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