The expression of the β-2 adrenergic receptor (β2AR), one of the stress-inducible receptors, has been reported to be closely correlated with malignant tumors. Prostate cancer is the most common non-cutaneous cancer among males, accompanied with increased castration levels and β2AR activation in patients. However, the role of β2AR activation in prostate cancer cells and its underlying mechanisms are not fully understood. Here, we found that β2AR activation promoted cell proliferation and cell migration through increasing cellular adenylyl cyclase (cAMP) levels and ERK1/2 activation in LNCaP and PC3 prostate cancer cells. Moreover, the scaffold protein β-arrestin2 was found to be involved in the β2AR-mediated activation of ERK1/2 and cell proliferation using stable overexpressing β-arrestin2 LNCaP (LNCaP-βArr2) cells. Furthermore, enhanced β-arrestin2/c-Src complex formation by β2AR activation was observed in LNCaP-βArr2 cells. In addition, the c-Src inhibitor could block this enhanced complex formation and suppressed cell proliferation. This study demonstrates that βArr2 is involved in prostate carcinogenesis induced by stress and provides potential therapeutic targets for cancer.

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