Androgen-induced differentiation and tumorigenicity of human prostate epithelial cells

Cancer Res. 2004 Dec 15;64(24):8867-75. doi: 10.1158/0008-5472.CAN-04-2938.

Abstract

Androgen ablation is the primary treatment modality for patients with metastatic prostate cancer; however, the role of androgen receptor signaling in prostate cancer development remains enigmatic. Using a series of genetically defined immortalized and tumorigenic human prostate epithelial cells, we found that introduction of the androgen receptor induced differentiation of transformed prostate epithelial cells to a luminal phenotype reminiscent of organ-confined prostate cancer when placed in the prostate microenvironment. Moreover, androgen receptor expression converted previously androgen-independent, tumorigenic prostate epithelial cells into cells dependent on testosterone for tumor formation. These observations indicate that androgen receptor expression is oncogenic and addictive for the human prostate epithelium.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androgens / metabolism
  • Androgens / physiology*
  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / physiology
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism
  • Cell Transformation, Neoplastic / pathology*
  • DNA-Binding Proteins
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Epithelial Cells / physiology
  • Gene Expression Profiling
  • Genes, ras / genetics
  • Humans
  • Male
  • Mice
  • Multigene Family
  • Prostate / metabolism
  • Prostate / pathology*
  • Prostate / physiology
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / biosynthesis
  • Receptors, Androgen / genetics
  • Receptors, Androgen / physiology*
  • Telomerase / genetics

Substances

  • Androgens
  • DNA-Binding Proteins
  • Receptors, Androgen
  • Telomerase