Preliminary Study On The Expression Of Runx3 Gene And DNA Methylation Regulatory Mechanism In Gastric Cancer

PartⅠExpression of Runt-related transcription factor 3 gene and DNA methyltransferase 1 and their correlations in gastric cancerObjective: To investigate the expressions and correlations with clinicopathological data of Runt-related transcription factor 3 gene (Runx3) and DNA methyltransferase 1 (Dnmt1) and to explore their clinical significance in human gastric cancer.Mathods: Reverse transcription-PCR (RT-PCR)was used to detect Runx3 mRNA and Dnmt1 mRNA expression level of samples of primary gastric cancer and corresponding non-cancerous gastric mucosa, which were obtained from surgically resection specimens of 70 patients. Western blot was used to detect the expression of Runx3 at protein levels.Result: RT-PCR showed that the expression of Runx3 in gastric carcinoma was significantly lower than that in normal mucosa (0.5749±0.3580 vs 1.7252±0.4085, P<0.05) , the expression of Dnmt1 in gastric cancer was higher than that in normal mucosa (3.3770±1.8498 vs 1.1186±0.3217, P<0.05). Western blot also showed that the protein expression of Runx3 in gastric carcinoma was significantly lower than that in normal mucosa (40132±16034 vs 96002±23046,P<0.05). The depression of Runx3 was correlated with the depth of invasion , TNM stage and pathologic differentiation degree(P<0.05). Correlation betwwen Dnmt1 expression and clinicopathological characteristics was not demonstrated in gastric cancer(P>0.05). The relationship between Runx3 and Dnmt1 expression is significant(r=-0.261, P<0.05) .Conclusion: Runx3 is downregulated, and Dnmt1 is overexpressed in gastrc cancer. The depression of Runx3 was correlated with the depth of invasion , TNM stage and pathologic differentiation degree. Runx3 expression is significantly negative correlated with Dnmt1 expression. PartⅡPreliminary study on DNA methylation regulates expression of Runx3 genes in human gastric cancerObjective: In this study,we detected expression of gene Runx3 and its promoter methylation status to evaluate the effect of Runx3 promoter methylation on Runx3 expression and its possible relationship with its clinicopathological characteristics of gastric cancer.Methods: The promoter methylation status was measureed by using MSP (methylation specific PCR).Results: The frequency of promoter methylation of Runx3 gene in gastric cancers was 40%(28/70),while 3% (2 of 70) of adjacent normal gastric mucosa was present with the promoter methylation. Methylation of Runx3 gene in gastric cancers was related with differentiation, tumor stage. There was also significance correlation between methylation of Runx3 and Runx3 mRNA and Dnmt1 mRNA (r=-0.408,P <0.01;r=0.64,P <0.01).Conclusion: The abnormal promoter methylation is one of the prodominant inactivation methanism of the Runx3 gene and may be associated with pathogenesis of human gastric cancer. Correlation between a high level of DNA methyltransferase 1 (Dnmt1) and Runx3 methylation was demonstrated . The result implied that Dnmt1was contributed to the progression of DNA methylation regulation of Runx3 genes in human gastric cancer.