CDKs和CKIs在胃癌细胞周期调控中的相关性

研究 CDKs和 CKIs在调节胃癌细胞周期进程中的作用表明 ,全反式视黄酸 ( ATRA)通过诱导细胞滞留在 G1/G0 期而抑制胃癌细胞生长 .Western blot分析显示 ,ATRA可上调 p2 1 waf1/ cip1的表达 ,而抑制 p1 6ink4 的表达 .免疫沉淀及活性测定表明 ,CDK2 激酶活性可被 ATRA抑制 ,而CDK4 活性先被诱导上升 ,2 4 h后逐渐下降 .另外 ,ATRA可以调节 Rb蛋白的磷酸化和 c- myc蛋白的表达 .由此证实 ,ATRA诱导胃癌细胞滞留于 G1/G0 期与其上调 p2 1 waf1/ cip1的表达和抑制CDK2 和 CDK4 激酶活性 ,进而抑制 Rb蛋白的磷酸化和 c- myc的表达有关 . Rb蛋白是 ATRA抑制胃癌细胞生长的下游调节因子 .另外 ,p1 6ink4 的功能在胃癌细胞中可能丧失 .

Relationship between CDKs and CKIs in Regulation of Cell Cycle Progression of Human Gastric Cancer Cells

The roles of CDKs and CDIs in regulation of cell cycle progression of human gastric cancer cells was investigated.The results demonstrated that ATRA(all trans retinoic acid) inhibited growth of gastric cancer cells through inducing cells arrest in G 1/G 0.Western blotting showed that p21 waf1/cip1 was up regulated by ATRA in gastric cancer cells,which resulted in a decreased CDK 2 activity,as revealed by immunoprecipitation assay.However,p16 ink4 ,which specifically inhibited cyclinD 1/CDK 4 complexes,was down regulated by ATRA both at mRNA and protein levels.By accompanying with another inhibitor p21 waf1/cip1 ,it led to the increase of CDK 4 activity after treatment of ATRA for 12 h,and the decrease after 24 h.As a result,Rb protein could be regulated in its phosphorylation state by ATRA.Furthermore expression of c myc was suppressed by ATRA.Taken together,the data indicate that induction of gastric cancer cells arrest in G 1/G 0 by ATRA was probably through up regulation of p21 waf1/cip1 ,which contributed to inhibition of CDK 2 and CDK 4 activities,then led to Rb phosphorylation chenges,associated with inhibition of c myc expression.Rb might be a downstream effector of ATRA in inhibition of gastric cancer cell growth.In addition,the function of p16 ink4 might be lost in gastric cancer cells.