Androgen receptor overexpression alters binding dynamics of the receptor to chromatin and chromatin structure.

Castration-resistant prostate cancers (CRPCs) overexpress often androgen receptor (AR). Here, we investigated the effect of AR overexpression on the dynamics of AR loading and RNA polymerase II (RNA Pol II) recruitment to chromatin. Acetylation of histone 3 (AcH3) on lysines 9 and 14 (K9 and K14) was also studied. We used an LNCaP-based AR overexpression cell line model that includes a control line and two sublines, LNCaP-ARmo and LNCaP-ARhi, which overexpress AR twofold to threefold and fourfold to fivefold, respectively. Cells were exposed to 1 or 100 nM of dihydrotestosterone (DHT). Chromatin immunoprecipitation (ChIP) on the promoters and enhancers of prostate specific antigen (PSA) and transmembrane protease, serine 2 (TMPRSS2) genes was performed. qRT-PCR was used to measure the levels of PSA and TMPRSS2 transcripts. Upon stimulation with 1 nM DHT, AR and RNA Pol II were recruited onto PSA and TMPRSS2 enhancer regions to a greater extent (P < 0.05) in AR-overexpressing cells compared to control cells. The difference in AR loading between the control and AR-overexpressing cells was abolished by a higher DHT concentration. The ratio of AcH3/H3 was increased in AR-overexpressing cells. The induction of transcription of PSA and TMPRSS2 occurred earlier in the AR-overexpressing cells. Our findings suggest that the levels of AR potentiate the recruitment of the AR, as well as components of the basic transcription machinery, to chromatin and affect the acetylation of histones in the presence of low levels of androgens. These changes result in enhanced gene transcription of AR target genes.

Urbanucci A ，Marttila S ，Jänne OA ，Visakorpi T ... -  《-》

Androgen receptor activity at the prostate specific antigen locus: steroidal and non-steroidal mechanisms.

Jia L ，Kim J ，Shen H ，Clark PE ，Tilley WD ，Coetzee GA ... -  《MOLECULAR CANCER RESEARCH》

Increased expression of androgen receptor sensitizes prostate cancer cells to low levels of androgens.

Waltering KK ，Helenius MA ，Sahu B ，Manni V ，Linja MJ ，Jänne OA ，Visakorpi T ... -  《-》

Integration of cap analysis of gene expression and chromatin immunoprecipitation analysis on array reveals genome-wide androgen receptor signaling in prostate cancer cells.

Takayama K ，Tsutsumi S ，Katayama S ，Okayama T ，Horie-Inoue K ，Ikeda K ，Urano T ，Kawazu C ，Hasegawa A ，Ikeo K ，Gojyobori T ，Ouchi Y ，Hayashizaki Y ，Aburatani H ，Inoue S ... -  《-》

Overexpression of androgen receptor enhances the binding of the receptor to the chromatin in prostate cancer.

Urbanucci A ，Sahu B ，Seppälä J ，Larjo A ，Latonen LM ，Waltering KK ，Tammela TL ，Vessella RL ，Lähdesmäki H ，Jänne OA ，Visakorpi T ... -  《-》