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

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.

• Authors: J H Dennis, V Budhram-Mahadeo, D S Latchman
• Journal: Oncogene (Oncogene) Vol. 20 Issue 36 Pg. 4961-71 (Aug 16 2001) ISSN: 0950-9232 [Print] England
• PMID: 11526481 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• DNA-Binding Proteins
• Estrogen Antagonists
• POU4F2 protein, human
• Selective Estrogen Receptor Modulators
• Transcription Factor Brn-3
• Transcription Factor Brn-3B
• Transcription Factors
• Tamoxifen
• Estradiol
• Thymidine

Topics

• Adenocarcinoma (metabolism, pathology)
• Breast Neoplasms (metabolism, pathology)
• Cell Division
• Cell Line, Transformed
• DNA-Binding Proteins (genetics, physiology)
• Estradiol (pharmacology)
• Estrogen Antagonists (pharmacology)
• Female
• Humans
• Selective Estrogen Receptor Modulators (pharmacology)
• Tamoxifen (pharmacology)
• Thymidine (metabolism)
• Transcription Factor Brn-3
• Transcription Factor Brn-3B
• Transcription Factors (genetics, physiology)
• Transfection
• Tumor Cells, Cultured