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The Brn-3b POU family transcription factor regulates the cellular growth, proliferation, and anchorage dependence of MCF7 human breast cancer cells

Oncogene volume 20, pages 4961–4971 (2001)Cite this article

Abstract

The Brn-3b POU domain containing transcription factor is expressed in the developing sensory nervous system as well as in epithelial cells of the breast, cervix, and testes. Brn-3b functionally interacts with the estrogen receptor (ER) and in association with the ER, regulates transcription from estrogen responsive genes. In addition, Brn-3b expression is elevated in breast tumours compared to levels in normal mammary cells. To explore the role of Brn-3b in breast cancer, we established stable cell lines derived from the MCF7 human breast cancer cell line which had been transfected with Brn-3b sense or anti-sense constructs. The Brn-3b over-expressing cell lines exhibited increased growth rate, reached confluence at a higher saturation density, had higher proliferative activity, and an enhanced ability to form colonies in soft agar when compared to the control empty vector transfected cells. Likewise, the Brn-3b anti-sense cell lines showed reduced cellular growth and proliferation, reached confluence at a lower density, and exhibited a decreased ability to form colonies in soft agar when compared to the vector controls. Five to ten per cent of the Brn-3b over-expressing cells exhibited a severely altered morphology characterized by reduced adherence to tissue culture plastic, increased cell size, and a vacuolar cell shape. These results thus further indicate a role for the Brn-3b transcription factor in regulating mammary cell growth and suggest that its elevation in breast cancer is of functional significance.

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Acknowledgements

We thank Tarik Moroy for the gift of pLTR and Brn-3b recombinant clones, Martin Smith for the gift of pJ4 Brn-3b anti-sense constructs, and Benjamin Chain and Walter Low for assistance with the proliferation studies. This work was supported by the USA Department of Defence, Breast Cancer Research Program.

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  1. Institute of Child Health, 30 Guilford Street, London, WC1N 1EH, UK

    Jonathon Hancock Dennis, Vishwanie Budhram-Mahadeo & David Seymour Latchman

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Dennis, J., Budhram-Mahadeo, V. & Latchman, D. The Brn-3b POU family transcription factor regulates the cellular growth, proliferation, and anchorage dependence of MCF7 human breast cancer cells. Oncogene 20, 4961–4971 (2001). https://doi.org/10.1038/sj.onc.1204491

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