Second messenger up‐regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines, PC‐3 and DU‐145

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Abstract
A theoretical pathway of transcriptional regulation of the androgen receptor (AR) gene is via a cAMP response element (CRE) present in its promoter region (−508 to −501). After 20 h of stimulation with 8‐bromo‐cAMP, AR mRNA was upregulated in LNCaP but not in either PC‐3 or DU‐145 cell lines. We have demonstrated that the level of CRE binding protein (CREB) was the same in all cell lines and that the putative AR‐CRE forms specific and competable protein interactions with CREB. The ability to regulate AR gene transcription via the second messenger pathway is lost in the PC‐3 and DU‐145 cell lines. This may be an important primary mechanism of androgen insensitivity in prostate cancer.