Prostate cancer (PCa) becomes lethal when cancer cells develop into castration-resistant PCa (CRPC). Androgen receptor (AR) gene mutation, altered AR regulation, or overexpression of AR often found in CRPC is believed to become one of the key factors to the lethal phenotype. Here we identify Slug, a member of the Snail family of zinc-finger transcription factors associated with cancer metastasis, as a unique androgen-responsive gene in PCa cells. In addition, the presence of constitutively active AR can induce Slug expression in a ligand-independent manner. Slug overexpression will increase AR protein expression and form a complex with AR. In addition, Slug appears to be a novel coactivator to enhance AR transcriptional activities and AR-mediated cell growth with or without androgen. In vivo, elevated Slug expression provides a growth advantage for PCa cells in androgen-deprived conditions. Most importantly, these observations were validated by several data sets from tissue microarrays. Overall, there is a reciprocal regulation between Slug and AR not only in transcriptional regulation but also in protein bioactivity, and Slug-AR complex plays an important role in accelerating the androgen-independent outgrowth of CRPC.
Written by:
Wu K, Gore C, Yang L, Fazli L, Gleave M, Pong RC, Xiao G, Zhang L, Yun EJ, Tseng SF, Kapur P, He D, Hsieh JT Are you the author?
5323 Harry Hines, J8-134, Dallas, Texas 75390. ; or Dalin He, 277 Yanta West Road, Xi'an 710061, China. E-mail:
Reference: Mol Endocrinol. 2012 Sep;26(9):1496-507
doi: 10.1210/me.2011-1360
PubMed Abstract
PMID: 22745193
