TY - JOUR
T1 - Endometrial cancer and hypermethylation
T2 - Regulation of DNA and MicroRNA by epigenetics
AU - Banno, Kouji
AU - Kisu, Iori
AU - Yanokura, Megumi
AU - Masuda, Kenta
AU - Kobayashi, Yusuke
AU - Ueki, Arisa
AU - Tsuji, Kosuke
AU - Yamagami, Wataru
AU - Nomura, Hiroyuki
AU - Susumu, Nobuyuki
AU - Aoki, Daisuke
PY - 2012
Y1 - 2012
N2 - Endometrial cancer is the seventh most common cancer in women worldwide. Therefore elucidation of the pathogenesis and development of effective treatment for endometrial cancer are important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic variation and mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, in recent years, epigenetic mechanisms that do not involve changes in DNA sequences have been examined. Studies aimed at detection of aberrant DNA hypermethylation in cancer cells present in microscopic amounts in vivo and application of the results to cancer diagnosis have also started. Breakdown of the DNA mismatch repair mechanism is thought to play a large role in the development of endometrial cancer, with changes in the expression of the hMLH1 gene being particularly important. Silencing of genes such as APC and CHFR, Sprouty 2, RASSF1A, GPR54, CDH1, and RSK4 by DNA hypermethylation, onset of Lynch syndrome due to hereditary epimutation of hMLH1 and hMSH2 mismatch repair genes, and regulation of gene expression by microRNAs may also underlie the carcinogenic mechanisms of endometrial cancer. Further understanding of these issues may permit development of new therapies.
AB - Endometrial cancer is the seventh most common cancer in women worldwide. Therefore elucidation of the pathogenesis and development of effective treatment for endometrial cancer are important. However, several aspects of the mechanism of carcinogenesis in the endometrium remain unclear. Associations with genetic variation and mutations of cancer-related genes have been shown, but these do not provide a complete explanation. Therefore, in recent years, epigenetic mechanisms that do not involve changes in DNA sequences have been examined. Studies aimed at detection of aberrant DNA hypermethylation in cancer cells present in microscopic amounts in vivo and application of the results to cancer diagnosis have also started. Breakdown of the DNA mismatch repair mechanism is thought to play a large role in the development of endometrial cancer, with changes in the expression of the hMLH1 gene being particularly important. Silencing of genes such as APC and CHFR, Sprouty 2, RASSF1A, GPR54, CDH1, and RSK4 by DNA hypermethylation, onset of Lynch syndrome due to hereditary epimutation of hMLH1 and hMSH2 mismatch repair genes, and regulation of gene expression by microRNAs may also underlie the carcinogenic mechanisms of endometrial cancer. Further understanding of these issues may permit development of new therapies.
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U2 - 10.1155/2012/738274
DO - 10.1155/2012/738274
M3 - Review article
C2 - 22548175
AN - SCOPUS:84861033736
JO - Biochemistry Research International
JF - Biochemistry Research International
SN - 2090-2247
M1 - 738274
ER -