Abstract:
Abstract:Objective:To study the effect of imbalance of proliferation and apoptosis in the development of colorectal carcinoma(CRC),and the molecular mechanism of the dynamic change.Methods:ORC was induced with dimethylhydrazine(DMH) in male mice of Kimming strain. The mice were killed in batches in the 12th,18th and 24th weeks of carcinoma induction. The distribution and extent of proliferation and apoptosis of the colorectal mucosa, at various intervals, were dynamically observed. Three genes,p21waf1,Bax and Gadd45 were analyzed by RT-PCR, immunohistochemistry and Western blot. Results:During the course of carcinoma induction,the mucosas of the model mice showed sequential changes of atypital hyperplasia,adenoma,and carcinoma. Compared with control group, the PCNA expression of the model group mice was significantly higher(P<0.01); and the expression was also progressively increased from normal mucosaatypital hyperplasiaadenomacarcinoma(P<0.01).The highest PCNA expression was observed in cancer.Meanwhile, the ratio of proliferation to apoptosis also progressively increased(P<0.01). The three genes , p21waf1,GADD45 and Bax were increased during the mucosa development from normal mucosa to adenoma,whereas their expression was very weak in cancer.Conclusions:During the mice colon carcinogenesis induced by DMH, the colorectal mucosa appears to be in a disequilibrium of proliferation and apoptosis; colon carcinogenesis is related to the 3 suppressor genes, p21waf1, GADD45 and Bax.