STAMP2 expression is exquisitely androgen regulated in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptor-negative prostate cancer cell lines PC-3 and DU145.
Prostate cancer progression to castration refractory disease is associated with anomalous transcriptional activity of the androgen receptor (AR) in an androgen-depleted milieu.
GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models.
Using our approach, we identified conditions in which AR was modulated in a large collection of microarray profiles from prostate cancer cell lines including (1) constitutively active mutants or knockdown of AR, (2) decreases in availability of androgens by castration or removal from media, and (3) exposure to chemical modulators that work through indirect mechanisms including suppression of AR expression.
These results further point out the important role of the AR in prostate tumors and support further testing of AR downregulation for treatment of prostate cancer.
We further found the association between PYK2, S6K1, and AR in their protein expression and phosphorylation levels among normal prostate PZ-HPV-7 cells and prostate cancer LNCaP and 22Rv1 cells.
Consistent with our hypothesis, a specific expression pattern with high levels of NRIP and AR, together with a low level of DDB2, was found more frequently in the human prostate cancer tissues with a cribriform pattern than in non-cribriform tumors, suggesting that disruption of the balance between NRIP and DDB2 may change AR protein homeostasis and contribute to pathogenesis in certain aggressive types of prostate cancer.
Deletion or mutation of the androgen receptor (AR) renders prostate tumors refractory to apoptosis by androgen ablation, the mainstay of prostate cancer therapy.
Within this review, we identify candidate molecules involved in diverse processes such as cell proliferation, death and apoptosis, signal transduction, androgen receptor (AR) signalling, cellular adhesion and angiogenesis that are linked to outcome in prostate cancer.
We report that re-expression of AR in PC-3 human prostate cancer cell line resulted in upregulation of IFI16 protein, a negative regulator of cell growth.
Marked response to cabazitaxel in prostate cancer xenografts expressing androgen receptor variant 7 and reversion of acquired resistance by anti-androgens.
The androgen-mediated repression of hTERT is abrogated in a human prostate cancer cell line exhibiting hormone-dependent growth, which expresses a mutant AR (T877A) frequently occurring in prostate cancer.
This mutant AR contains two mutations (L701H and T877A) and was previously reported as a high-affinity cortisol/cortisone responsive AR (AR(ccr)) isolated from the androgen-independent human prostate cancer cell lines MDA PCa 2a and 2b (Zhao et al.Nature Med.2000, 6, 703-6).
Expressions of epithelial-to-mesenchymal transition (EMT) and stem cell markers were molecularly tested using prostate cancer (PCa) cells transfected with AR and AR3 (also known as AR-V7) plasmids or siRNA, and also cultured cells under androgen deprivation therapy (ADT) condition.