Caveolin-1 overexpression enhances androgen-dependent growth and proliferation in the mouse prostate

Int J Biochem Cell Biol. 2011 Sep;43(9):1318-29. doi: 10.1016/j.biocel.2011.04.019. Epub 2011 May 12.

Abstract

Prostate cancer (PCa) continues to be one of the leading causes of cancer-related deaths among American men. The prostate relies upon the androgen receptor (AR) to mediate the effects of androgens on normal growth, a reliance that is maintained during malignant prostate growth. Caveolin-1 (Cav-1), the main structural component of caveolae, has been shown to promote the malignant growth and invasion of prostate tumors. In vitro work has shown that Cav-1 can act as an AR coactivator by enhancing its transciptional activity. However, it is unknown how Cav-1 affects androgen-dependent growth and signaling in vivo. To explore this role, a novel mouse model of Cav-1 overexpression was developed with a hormone-insensitive promoter. Cav-1 transgenic (Tg) mice subjected to castration and androgen stimulation display enlarged prostate weights and increased DNA synthesis. Through gene transcript and proteomic profiling, we demonstrate that Cav-1 overexpression favors androgen-regulated responses and enhances processes involved in transcription, cell cycle progression and protein synthesis. Interestingly, Cav-1 overexpression was associated with an increase in the phosphorylation of AR on serine 210, a post-translational modification linked to its activity under androgen-stimulated conditions. In addition, these mice exhibited an increase in the phosphorylation of ribosomal S6 protein on serine 235/236 (pS6), a marker of protein synthesis and a downstream component of the mTOR pathway. Thus, Cav-1 Tg mice could serve as a novel model for studying AR-regulated pathways involved in prostate growth and proliferation.

Publication types

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

MeSH terms

  • Animals
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Nucleus / metabolism
  • Cell Proliferation*
  • DNA-Binding Proteins / metabolism
  • Epithelium / metabolism
  • Female
  • Gene Expression Profiling
  • Gene Expression*
  • Genes, Neoplasm
  • Male
  • Mice
  • Mice, Transgenic
  • Minichromosome Maintenance Complex Component 7
  • Nuclear Proteins / metabolism
  • Orchiectomy
  • Organ Size
  • Phosphorylation
  • Prostate / cytology
  • Prostate / growth & development*
  • Protein Transport
  • Proteome / genetics
  • Proteome / metabolism
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Testosterone / pharmacology*
  • Testosterone / physiology
  • Transcriptional Activation

Substances

  • Caveolin 1
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Proteome
  • Receptors, Androgen
  • Testosterone
  • TOR Serine-Threonine Kinases
  • mTOR protein, mouse
  • Mcm7 protein, mouse
  • Minichromosome Maintenance Complex Component 7