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.
Key words
Cyclin dependent kinase /
Cyclin dependent kinase inhibitor /
Cell cycle /
Gastric cancer cell /
All trans retinoic acid
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