Protein expression, mRNA expression and gene amplification of DNA methyltransferase 1 in endometrial tumor tissues.

Inactivation of tumor suppressor genes by methylation is an important pathway in the multi-step process of carcinogenesis. This aim of this study was to investigate the expression of DNA methyltransferase 1 (DNMT1) which strongly contributes to the methylation process in endometrial normal and tumor tissues. Moreover, a correlation with the expression of hMLH1 and E-cadherin that was inactivated in a number of endometrial cancers was observed. Samples were obtained from 8 cases of normal endometrium, 10 cases of hyperplasia, 11 cases of atypical hyperplasia and 38 cases of carcinoma. DNMT1 expression was correlated with tumor progression (P=0.0023), as well as with the attenuation of hMLH1 and E-cadherin expression (P=0.031 and 0.031, respectively). No attenuation of hMLH1 and E-cadherin expression was observed in DNMT1-negative cases. Thus, the investigation of DNMT1 expression in clinical samples was shown to be useful in identifying the conditions that are related to general methylation. Overexpression of DNMT1 microRNA (mRNA) was mainly observed in carcinomas. Gene amplification occurred with tumor development. Gene amplification of DNMT1 was correlated with the expression of DNMT1 protein (P=0.041). In conclusion, overexpression of DNMT1 protein is caused by various factors, one of which is gene amplification.