Apoptosis Dysregulation in Human Gastric Carcinomas: Relationship to Anti- and Pro-Apoptotic Protein Expression


Apoptosis and the genes regulating this process have recently become a focus of interest in the study ofcancer development and progression. Both Bcl-2 and Bax are transcriptional targets for the tumor supressorprotein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. The coordinate performanceof these molecules is crucial for controlling life or death of a cell. Correlations between apoptosis and proteinexpression of genes controlling this process including Bcl-2, Bax and p53 in gastric cancer were here investigatedwith gastric tumor samples of forty patients . DNA ploidy pattern was anlyzed using flow cytometry and Bcl-2,Bax, and p53 were immunohistochemically localized using specific monoclonal antibodies. In addition, serumBcl-2 protein was estimated by enzyme linked immunosorbant assay (ELISA). The obtained data showed thatthe mean serum Bcl-2 protein concentration demonstrated a significant increase (P<0.0001) in positive cases(61.5±11.0 unit/ml) compared to the negative ones (47.5±3.5 unit/ml). Serum Bcl-2 protein positivity was detectedin 13/40 of gastric cancer patients. Immunohistochemical positivity for Bcl-2, Bax, and p53 was shown in 45%,68%, and 63% of samples, respectively. Positive Bcl-2 and p53 immunostaining was significantly linked withthe histological grade (P<0.02 and P<0.009 respectively) and lymph duct invasion (P<0.02 and P<0.001 ). On theother hand, Bax was significantly differed with lymph duct invasion and the ploidy pattern (P<0.03 and P<0.002).In conclusion, the apoptosis-related genes p53, Bcl-2, and Bax are all linked to the occurrence of gastric cancer.Therefore, analysis of their expressions may add useful information concerning tumor behavior.