| IntroductionGastric carcinoma is the most frequent malignant tumor in China, and one of the commonest in the world. The etiologies of stomach cancer are multiple and vary with the race, geography and dietary habits. Although the underlying molecular mechanisms leading to the malignant transformation need to be further elucidated, it is apparent that during gastric carcinogenesis, the intrinsic regulatory systems for normal cell survival and death is disordered, resulting in an unrestricted proliferation status. Therefore, a better understanding of the signal transduction associated with cell proliferation and apoptosis in gastric epithelial cells would be of importance in prevention and treatment of gastric cancers.Fas receptor ( CD95/Apo - 1) is one of the most important members in the TNF receptor superfamily. The interaction of Fas and its ligand ( FasL) results in transduction of a cytolytic signal into the cell, regulating cell survival and death. Fas/FasL system is one of the substantial elements in carcinogenesis and development. Several studies indicated that phosphorylation - based MAPK cascade could be involved in both inhibition and activation of Fas - mediated apoptosis. The mitogen - activated protein kinase ( MAPK) pathway is involved in regulation of cell proliferation and differentiation, as well as in various metabolic functions. Extracellular signal - regulated kinase( ERK) could promote cell survival by inhibition of apoptosis. While, Jun Kinase (JNK) is required for induction of apoptosis. However, there is few systematic understand about the function of MAPK in Fas - induced apoptosis in gastric carcinogenesis. In this paper, we study whether MAPK, especially ERK, could play a significant role or not in Fas - induced apoptosis, leading to the intrinsic regulatory system for cell survival and death disordered in gastric cancers.Materials and MethodsCell culture: gastric cancer cell line SGC - 7901 cells were cultured in DMEM supplemented with 10% FCS with 5% CO2 in air at 37C.Tested ERK activity in SGC - 7901 cells treated with anti - Fas Ab or PD98059 pretreatment by advanced Takai method.Western blot hybridization with anti - active ERK/JNK pAb.FACScan flow cytometer to test apoptotic cells.Statistical analysis with SPSS10.0.ResultsEffect of anti - Fas Ab on the activity of ERK by isotope:The activity of ERK increases to the peak at 30min of anti - FasAb treatment. In PD98059 pretreatment groups, ERK activity is lowerthan control group.Western blot hybridization with anti - active ERK pAb:The same as the results of isotope method, the activity of ERKreaches to the peak at 30min.Effect of anti - Fas Ab on the activity of JNK:The activity of JNK has no evident change among samples.FACScan flow cytometer:The number of sub - G1 cell is (30.49 +2.598)% in PD98059 and and - Fas Ab cotreatment group, which is higher than and - Fas Ab treatment group and control group respectively.DiscussionThe most important characteristic of cancer is that cell apoptosis decreases greatly and cell proliferation unlimitedly. Immune system couldnt effectively kill tumor cells and tumor cells could survival by escaping from immune surveillance and reducing immune responses. Many studies indicated that Fas/FasL system plays a key role in im-muno - escape of cancer cells. Fas - mediated apoptosis is the main way of cy to toxic effect induced by immune responses.It has been suggested that cancer cells have developed several strategies to escape the immune surveillance by turning down Fas -mediated apoptodc pathway, one strategy clearly being ERK - dependent protection. ERK pathway plays a critical role in cell proliferation, differentiation, death, carcinogenesis, etc. Recendy it has been reported that the constitutive activation of ERK occurs in a wide variety of human tumor tissues'. Bang et al. reported that increased ERK activity was associated with human gastric adenocarcinoma.Our data indicated that in the absence of any specific tre...
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