c-Jun enhancement of androgen receptor transactivation is associated with prostate cancer cell proliferation

Oncogene. 2006 Nov 16;25(54):7212-23. doi: 10.1038/sj.onc.1209705. Epub 2006 May 29.


Androgens and the androgen receptor (AR) are involved in the growth and progression of prostate cancer. Our previous studies suggest that the proto-oncoprotein c-Jun is an AR coactivator that stimulates AR transactivation by mediating receptor dimerization and subsequent DNA binding. To study the physiological relevance of this c-Jun activity on AR, we have generated stable LNCaP cell lines expressing different levels of c-Jun. These cell lines exhibit a direct correlation between endogenous c-Jun levels and AR transcriptional activity and expression of endogenous androgen-regulated genes. Disruption by antisense RNA of endogenous c-Jun expression in LNCaP cells strongly compromises the androgen-dependent proliferation of these cells. In contrast, expression of a c-Jun mutant, which is fully active in coactivation of AR but deficient in AP-1 transactivation, significantly enhances androgen-dependent proliferation. This finding indicates that the coactivation function of c-Jun is sufficient for regulating androgen-induced growth of LNCaP cells. c-Jun also enhances AR transactivtion in androgen-independent LNCaP cells, which closely mimic hormone-refractory prostate cancer cells in gene expression and growth behavior. Importantly, siRNA-mediated repression of endogenous c-Jun expression results in markedly reduced growth of these cells, strongly suggesting an important biological role for c-Jun in hormone-refractory prostate cancer.

Publication types

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

MeSH terms

  • Blotting, Northern
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation*
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Male
  • Prostatic Neoplasms / metabolism*
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Messenger / analysis
  • RNA, Small Interfering
  • Receptors, Androgen / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factor AP-1 / metabolism
  • Transcriptional Activation
  • Transfection


  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • RNA, Small Interfering
  • Receptors, Androgen
  • Transcription Factor AP-1