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AKT Regulates Androgen Receptor-dependent Growth and PSA Expression in Prostate Cancer

  • Margarita Mikhailova
  • Yu Wang
  • Roble Bedolla
  • Xiao-Hua Lu
  • Jeffrey I. Kreisberg
  • Paramita M. Ghosh
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Summary

Recurrent prostate cancer (PC) is usually treated with androgen deprivation therapy, which, despite initial success, eventually fails due to the development of androgen-independent PC. Androgen deprivation stimulates a significant increase in the phosphorylation (activation) of Akt, a serine/threonine kinase, which regulates cell growth and survival. Hence, we asked whether the increase in Akt phosphorylation contributes to the development of androgen independence. Akt regulates transcriptional activity of the androgen receptor (AR), and our data show that Akt-stimulated AR transcriptional activity is dependent on androgen-binding to the AR. PC proliferation has both androgen-sensitive and insensitive components. The androgen sensitive component is Akt-dependent, while the androgen-insensitive is not. However, Akt-induced cell survival is largely AR independent, suggesting that the cell stimulates Akt phosphorylation when subjected to androgen deprivation as an alternate pathway to maintain survival.

Keywords

Prostate Cancer Androgen Receptor Androgen Deprivation Therapy LNCaP Cell Recurrent Prostate Cancer 
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

  • Margarita Mikhailova
  • Yu Wang
  • Roble Bedolla
  • Xiao-Hua Lu
  • Jeffrey I. Kreisberg
  • Paramita M. Ghosh
    • 1
  1. 1.Research ServicesVA Northern California HCSMatherUSA

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