| Gastric carcinoma is one of the most common malignant tumors in the worldand the mortality of it is very high,but the diagnose ratio of early stage is so low.Global statistical report released by the World Health Organization (WHO), the annual incidence rate of gastric cancer in the world is 13.86%/10 million, second only to lung cancer.China is a high incidence area of gastric cancer; 400 thousand new cases of gastric cancer were discovered each year, accounting for 42% of the total number of patients with gastric cancer in the world.Malignant tumor is a serious threat to human life and health.According to WHO, cancer will replace the cardiovascular disease as the world’s largest number of deaths.The incidence of gastric cancer in Asia and South American countries is much higher than that in the United States and other Western European countries.The pathogenesis of gastric cancer is still not very clear, for the basic research of gastric cancer is more and more attention.Because of the high incidence of gastric cancer, the age is mainly concentrated in the middle-aged and elderly population. Therefore,the establishment of an aging animal model to study the physiological and pathological changes of gastric mucosal cells provides a unique way of thinking.lt will be helpful for the simulation of aging and the occurrence of gastric lesions and gastric cancer.Werner Syndrome (WS)-a rare autosomal recessive disorder with an incidence of approximately 10 per million individuals-has been considered as an ideal model for aging study. In order to produce WS mouse model, wrn and telomerase gene were double knockout. The cyclin-dependent kinase inhibitor P21 (Cdknla) promotes cell cycle arrest in response to many stimuli. Previous studies showed that p21 played an important role in the DNA damage signaling induced by telomere dysfunction. However, the relationship between p21 and aging-related apoptosis is still obscure. In this study, we crossed late-generation telomerase RNA component knockout mice (G2 or G3 mTerc-/-) carrying double homozygous deletion of WRN and Cdknla which with same generation telomerase knockout mice G2 or G3 mTerc-/-Wrn-/-p21-/-.The resulting offspring of G3mTer-/-Wrn-/- and G3 mTerc-/-Wrn-/-p21-/-mouse embryonic fibroblasts (MEFs) were used to analyze the expression of proteins associated with apoptosis by western blot. They were used to study functional effects in mitochondrial membrane potential, cell apoptosis rates by flow cytometry, and DNA damage via immunofluorescence assays. We showed that p21 function deficiency enhanced apoptosis and DNA damage of MEFs as we studied.In addition, the tissues of gastric in G4 mTer-/-Wrn-/-p21-/- were explored senescence by SA-β-Gal staining. We found that loss of p21 function could not rescue senescence of gastric and accelerate senescence of gastric. Besides, the cell proliferationrate of gastric were detectedby BrdU incorporation in G4 mTer-/-Wrn-/-p21-/-/. Interestingly, the results told us the cell proliferation rate of gastric obviously improved.Our results may provide an experimental basis for understanding the different levels of aging among mammalian. |
PDF Full Text Request