title: Carcinogenic mechanisms of endometrial cancer: involvement of genetics and epigenetics.
abstract: Endometrial cancer is increasing worldwide and the number of patients with this disease is likely to continue to grow, including younger patients. Many endometrial cancers show estrogen-dependent proliferation, but the carcinogenic mechanisms are unknown or not completely explained beyond mutations of single oncogenes and tumor suppressor genes. Possible carcinogenic mechanisms include imbalance between endometrial proliferation by unopposed estrogen and the mismatch repair (MMR) system; hypermethylation of the MMR gene hMLH1; mutation of PTEN, β-catenin and K-ras genes in type I endometrial cancer and of HER-2/neu and p53 genes in type II endometrial cancer; hypermethylation of SPRY2, RASSF1A, RSK4, CHFR and CDH1; and methylation of tumor suppressor microRNAs, including miR-124, miR-126, miR-137, miR-491, miR-129-2 and miR-152. Thus, it is likely that the carcinogenic mechanisms of endometrial cancer involve both genetic and epigenetic changes. Mutations and methylation of MMR genes induce various oncogenic changes that cause carcinogenesis, and both MMR mutation in germ cells and methylation patterns may be inherited over generations and cause familial tumorigenesis. Determination of the detailed carcinogenic mechanisms will be useful for prevention and diagnosis of endometrial cancer, risk assessment, and development of new treatment strategies targeting MMR genes.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.forename: Megumi
authors.initials: M
authors.lastname: Yanokura
authors.forename: Miho
authors.initials: M
authors.lastname: Iida
authors.forename: Kenta
authors.initials: K
authors.lastname: Masuda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D063646:Carcinogenesis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D019175:DNA Methylation; D053843:DNA Mismatch Repair; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism; D053842:Microsatellite Instability; D008954:Models, Biological; D009154:Mutation; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D009363:Neoplasm Proteins
keywords: DNA hypermethylation; DNA mismatch repair; endometrial cancer; epigenetics; genetics