摘要
Objective.To investigate PTEN expression and loss of heterozygosity(LOH)of its epigenetic microsatel-lites in gastric carcinoma and explore their roles in tumorigenesis and progression of gastric carcinoma.Methods.LOH of epigenetic microsatellites of PTEN(D10S541,D10S583and D10S1687)was exam-ined in advanced gastric carcinomas(n=56)by PCR-SSCP.The mRNA and protein expressions of PTEN gene were evaluated in normal mucosa(n=56),early(n=11)and advanced carcinomas(n=56)of the stomach using RT?PCR and immunohistochemoistry respectively.PTEN mRNA and protein expressions were compared with clinicopathological staging and lymph node metastasis of tumors.The relationship be-tween PTEN mRNA expression and LOH of microsatellites was discussed,as well as relationship between PTEN mRNA and protein expression.Results.LOH of D10S541,D10S583and D10S1687was found in28.6%(16/56)of advanced gas-tric carcinomas.The positive rates of PTEN expression were80.4%(45/56),45.5%(5/11)and32.1%(18/56)in normal gastric mucosa,early and advanced gastric carcinomas at mRNA level,while78.6%(44/56),36.4%(4/11)and28.6%(16/56)at protein level.PTEN mRNA and protein were less fre-quently expressed in early and advanced gastric carcinomas than normal gastric mucosa(P<0.05).There was negative correlation between PTEN mRNA expression and LOH of microsatellites(P<0.05).PTEN protein expression paralleled to its mRNA expression(P<0.05).The PTEN mRNA and protein expres-sions were negatively correlated with lymph node metastasis of advanced gastric carcinomas(P<0.05).Conclusion.Down?regulated expression of PTEN and frequent LOH of its epigenetic microsatellites might play an important role in gastric carcinogenesis.Reduced PTEN mRNA expression was closely as-sociated with LOH of its epigenetic microsatellites.Altered expression of PTEN might contribute to lymph node metastasis of gastric carcinoma by decreasing cell adhesion and apoptosis,increasing angiogenesis and cell mobility.
基金
ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina(No.30070845and30371607)
