MEK1 and MEK2 differentially regulate human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation  

作　　者：LIU Shan-ying LIANG Ying LIN Tian-xin SU Fang LIANG Wei-wen Uwe Heemann LI Yan 

机构地区：[1]Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong Higher Education Institutes,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,China [2]Department of Endocrinology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou,Guangdong 510120,China [3]Department of Nephrology,Technical University Munich,81675 Munich,Germany

出　　处：《Chinese Medical Journal》2012年第23期4197-4201,共5页中华医学杂志（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China （No. 81070598）.

摘　　要：Background Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase （MEK） 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells. Methods In the absence or presence of a selective inhibitor for MEK1 （PD98059） or a specific siRNA for MEK2 （siMEK2）, with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit （CCK）-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting. Results T24 cell proliferation was promoted by PD98059 at 5-20 IJmol/L, inhibited by siMEK2 at 25-100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERKI/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERKI/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected. Conclusion MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.Background Increased risk of bladder cancer has been reported in diabetic patients. This study was to investigate the roles of mitogen-activated protein kinase kinase （MEK） 1 and 2 in the regulation of human insulin- and insulin glargine-induced proliferation of human bladder cancer T24 cells. Methods In the absence or presence of a selective inhibitor for MEK1 （PD98059） or a specific siRNA for MEK2 （siMEK2）, with or without addition of insulin or glargine, T24 cell proliferation was evaluated by cell counting kit （CCK）-8 assay. Protein expression of MEK2, phosphorylation of ERK1/2 and Akt was analyzed by Western blotting. Results T24 cell proliferation was promoted by PD98059 at 5-20 IJmol/L, inhibited by siMEK2 at 25-100 nmol/L. PD98059 and siMEK2 remarkably reduced phosphorylated ERKI/2. Insulin- and glargine-induced T24 cell proliferation was enhanced by PD98059, suppressed while not blocked by siMEK2. Insulin- and glargine-induced ERKI/2 activation was blocked by PD98059 or siMEK2 treatment, whereas activation of Akt was not affected. Conclusion MEK1 inhibits while MEK2 contributes to normal and human insulin- and insulin glargine-induced human bladder cancer T24 cell proliferation.

关 键 词：insulin GLARGINE PROLIFERATION bladder cancer MEK 

分 类 号：R737.14[医药卫生—肿瘤]