Tyk2促进前列腺癌细胞系雄激素受体特异位点Tyr-267磷酸化  

Tyrosine kinase 2 facilitates site-specific tyrosine phosphorylation of androgen receptor for Tyr-267 in prostate cancer cell lines

作　　者：崔衢[1] 刘静[1] 张静[2] 王雅杰[3] 张勇[4] 崔竹梅[2] 刘元波[1] 

机构地区：[1]首都医科大学附属北京天坛医院血液内科,山东青岛266003 [2]青岛大学附属医院妇产科,山东青岛266003 [3]首都医科大学附属北京天坛医院临床医学实验室,山东青岛266003 [4]首都医科大学附属北京天坛医院泌尿外科,北京100050

出　　处：《基础医学与临床》2016年第11期1499-1504,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金(81272842);国家自然科学基金青年基金(81500157);北京天坛医院青年基金(20141

摘　　要：目的探讨JAK激酶家族成员Tyk2在雄激素受体(AR)磷酸化和前列腺癌细胞增殖中的作用。方法以LNCaP及LAPC-4细胞系为研究对象,在无雄激素条件下,用表皮生长因子(EGF)刺激,给予AIM-100/Baricitinib(INCB 028050)处理,免疫沉淀法和Western blot法检测AR磷酸化;将Tyk2 siRNA转染LNCaP及LAPC-4细胞系,用Western blot法检测沉默Tyk2对AR磷酸化的影响;用CCK-8试剂盒检测前列腺癌细胞增殖。结果 EGF诱导AR Tyr-267特异位点磷酸化并促进前列腺癌细胞增殖(P<0.05);AIM-100抑制Ack1和Tyk2介导的LNCaP/LAPC-4细胞增殖(P<0.05)和AR Tyr-267位点磷酸化;INCB抑制Tyk2磷酸化、AR Tyr-267位点磷酸化及LNCaP/LAPC-4细胞增殖(P<0.05)。结论 Tyk2是EGF诱导AR Tyr-267特异位点磷酸化和前列腺癌细胞增殖的关键激酶,在前列腺癌发病过程中可能扮演重要角色。Objective To investigate the effect of the JAK family member Tyk2 on androgen receptor（ AR） phosphorylation and the proliferation of prostate cancer cells. Methods LNCa P and LAPC-4 cell lines as subjects were incubated AIM-100 / Baricitinib（ INCB 028050） management,immunoprecipitation and / or Western blot was used to observe AR phosphorylation. RNA interference targeted silence Tyk2 gene was transfected into LNCa P and LAPC-4 cell lines. Western blot was used to observe the effect on AR phosphorylation. CCK-8 was used to measure cell proliferation. Results EGF can induce AR phosphorylation at Tyr-267 and proliferation of prostate cancer cells（ P〈0. 05）. AIM-100 inhibited the proliferation of prostate cancer cells（ P〈0. 05）,and AR Tyr-267 phosphorylation mediated by Ack1 and Tyk2. However,INCB inhibited Tyk2 phosphorylation and AR Tyr-267 phosphorylation as well as the proliferation of prostate cancer cells（ P〈0. 05）. Conclusions The JAK family member Tyk2 played a critical role in facilitating EGF-induced AR site-specific phosphorylation at Tyr-267 and in promoting prostate cancer cell proliferation.

关 键 词：雄激素受体 前列腺癌 磷酸化 Tyk2激酶 EGF 

分 类 号：R737.25[医药卫生—肿瘤]