Roles of ARA55 and ARA55-estrogen receptor β signaling pathway on the prostate cancer

Objective: To investigate the effect of ARA55 over-expression on the prostate cancer proliferation, aggression and apoptosis; to investigate whether ARA55 can regulate the expression of TGF-β or Smad7 in prostate cancer cells, and its relationship with estrogen receptor. Methods: The expression of ARA55, estrogen receptor α (ERα), ERβ, TGF-β and Smad7 was detected in human prostate cancer tissues, benign prostate hyperplasia tissues and normal prostate tissues using immunochemistry. In vitro, the human prostate cancer cell lines, LNCaP and DU-145, were cultured, and transfected with pEGFP-ARA55, then the bio-behaviors of the ARA55 over-expression cells were evaluated, including the proliferation, aggression and apoptosis. Lastly, the expression of TGF-β and Smad7 in prostate cancer cells with both ARA55 over-expression and ERβ knockout was detected by western blot. Results: The immunochemical results indicated that the expression of ARA55 was significantly lower in prostate cancer tissues than that in the benign prostate hyperplasia and normal prostate tissues. The cell experiment revealed that, both in the LNCaP cells and DU-145 cells, the proliferation and aggression of cells with ARA55 over-expression was much lower than the control groups, respectively; while the apoptosis rate of cells with ARA55 over-expression was higher than the control groups, suggesting that ARA55 could inhibit the prostate cancer proliferation and aggression. The expression of TGF-β was decreased when the ARA55 over-expression in DU-145 cells; whereas the down-regulation of TGF-β was eliminated, when the ERβ was knocked out in the cells with ARA55 over-expression. Conclusion: In prostate cancer, the expression of ARA55 was decreased, while the expression of ERα/β, TGF-β and Smad7 was increased. Furthermore, ARA55 could inhibit the TGF-β level via the ERβ signaling pathway, to inhibit the cancer cell proliferation and aggression. Therefore, ARA55 could be considered as one of the treatment targets.