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ERK/MAPK Regulation of the Androgen Responsiveness of Breast Cancer Cells

  • Diana G. Azzam
  • Jasmine W. T. Tay
  • Melissa A. Greeve
  • Jennet M. Harvey
  • Jacqueline M. Bentel
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Summary

The androgen receptor (AR) is the most widely expressed steroid hormone receptor in human breast cancers and androgens including 5α-dihydrotestosterone are potent inhibitors of breast cancer cell proliferation. The extracellular signal-regulated mitogen activated protein kinase (ERK/MAPK) pathway is hyperactivated in a proportion of breast tumors and can interact with steroid hormone receptor signaling by altering receptor phosphorylation, turnover, ligand, and cofactor interactions. To examine the effects of ERK/MAPK hyperactivity on AR levels, MCF-7 cells were stably transfected with a plasmid encoding a constitutively active MEK1 protein to create MCF-7-ΔMEK1 cells. Treatment of MCF-7-ΔMEK1 with androgens caused a transient increase in AR protein levels, similar to that observed in untransfected MCF-7 cells treated with androgens. Androgens also inhibited the proliferation of MCF-7-ΔMEK1 cells by 50–60% following 8 days of treatment in association with increased accumulation of cells in the G1 phase of the cell cycle. These results indicate that although ERK/MAPK hyperactivation in breast cancer cells is associated with reduced estrogen receptor (ERα) levels and antiestrogen resistance, AR levels are maintained and breast cancer cells remain susceptible to the growth inhibitory effects of androgens.

Keywords

Androgen Receptor Androgen Receptor Expression Breast Cancer Cell Proliferation Androgen Receptor Signaling Testosterone Propionate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • Diana G. Azzam
    • 1
  • Jasmine W. T. Tay
  • Melissa A. Greeve
  • Jennet M. Harvey
  • Jacqueline M. Bentel
  1. 1.Department of PathologyRoyal Perth HospitalPerth

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