TY - JOUR
T1 - Slug, a unique Androgen-regulated transcription factor, coordinates androgen receptor to facilitate castration resistance in prostate cancer
AU - Wu, Kaijie
AU - Gore, Crystal
AU - Yang, Lin
AU - Fazli, Ladan
AU - Gleave, Martin
AU - Pong, Rey Chen
AU - Xiao, Guanghua
AU - Zhang, Linlin
AU - Yun, Eun Jin
AU - Tseng, Shu Fen
AU - Kapur, Payal
AU - He, Dalin
AU - Hsieh, Jer Tsong
PY - 2012/9
Y1 - 2012/9
N2 - 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 andARnot only in transcriptional regulation but also in protein bioactivity, and Slug-AR complex plays an important role in accelerating the androgenindependent outgrowth of CRPC.
AB - 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 andARnot only in transcriptional regulation but also in protein bioactivity, and Slug-AR complex plays an important role in accelerating the androgenindependent outgrowth of CRPC.
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U2 - 10.1210/me.2011-1360
DO - 10.1210/me.2011-1360
M3 - Article
C2 - 22745193
AN - SCOPUS:84865582502
SN - 0888-8809
VL - 26
SP - 1496
EP - 1507
JO - Molecular Endocrinology
JF - Molecular Endocrinology
IS - 9
ER -