β-arrestin2 mediates β-2 adrenergic receptor signaling inducing prostate cancer cell progression

被引：42
作者：
Zhang, Penghui [2 ,3 ,4 ,5 ]
He, Xiaoyan [1 ,3 ,4 ,5 ]
Tan, Junjie [1 ,3 ]
Zhou, Xaoyan [1 ,3 ]
Zou, Lin [1 ,3 ,4 ,5 ]
机构：
[1] Chongqing Med Univ, Childrens Hosp, Ctr Clin Mol Med, Chongqing 400014, Peoples R China
[2] Chongqing Med Univ, Childrens Hosp, Clin Lab Ctr, Chongqing 400014, Peoples R China
[3] Chongqing Med Univ, Childrens Hosp, Minist Educ, Key Lab Child Dev Dis & Disorders, Chongqing 400014, Peoples R China
[4] Chongqing Med Univ, Childrens Hosp, Key Lab Pediat Chongqing, Chongqing 400014, Peoples R China
[5] Chongqing Med Univ, Childrens Hosp, Chongqing Int Sci & Technol Cooperat Ctr Child De, Chongqing 400014, Peoples R China
来源：
ONCOLOGY REPORTS | 2011年 / 26卷 / 06期
基金：
中国国家自然科学基金;
关键词：
prostate cancer; beta-2 adrenergic receptor; beta-arrestin2; Src; PROTEIN-COUPLED RECEPTORS; SRC TYROSINE KINASE; BETA-ARRESTIN; C-SRC; ACTIVATION; DESENSITIZATION; ENDOCYTOSIS; EXPRESSION; ROLES; RESENSITIZATION;
D O I：
10.3892/or.2011.1417
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
The expression of the beta-2 adrenergic receptor (beta 2AR), 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 beta 2AR activation in patients. However, the role of beta 2AR activation in prostate cancer cells and its underlying mechanisms are not fully understood. Here, we found that beta 2AR 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 beta-arrestin2 was found to be involved in the beta 2AR-mediated activation of ERK1/2 and cell proliferation using stable overexpressing beta-arrestin2 LNCaP (LNCaP-beta Arr2) cells. Furthermore, enhanced beta-arrestin2/c-Src complex formation by beta 2AR activation was observed in LNCaP-beta Arr2 cells. In addition, the c-Src inhibitor could block this enhanced complex formation and suppressed cell proliferation. This study demonstrates that beta Arr2 is involved in prostate carcinogenesis induced by stress and provides potential therapeutic targets for cancer.
引用
收藏
页码：1471 / 1477
页数：7
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