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Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis
Liao, Xiaoyun1,2; Siu, Michelle Kwan-Yee1; Chan, Kelvin Yuen-Kwong1; Wong, Esther Shuk-Ying1; Ngan, Hextan Yuen-Sheung3; Chan, Queeny Kwan-Yi1; Li, Albert Siu-Ming1; Khoo, Ui-Soon1; Cheung, Annie Nga-Yin1
关键词DNA hypermethylation endometrial cancer DNMT1 RASSF1A RASSF2A hDAB2IP BLU
刊名INTERNATIONAL JOURNAL OF CANCER
2008-07-15
DOI10.1002/ijc.23494
123期:2页:296-302
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Oncology
研究领域[WOS]Oncology
关键词[WOS]ABERRANT PROMOTER METHYLATION ; TUMOR-SUPPRESSOR GENE ; PROTEIN HDAB2IP GENE ; FREQUENT EPIGENETIC INACTIVATION ; GLUTATHIONE-S-TRANSFERASE ; MULTIPLE CPG ISLANDS ; HUMAN CANCER-CELLS ; K-RAS ; DNMT1 PROTEIN ; PROSTATE-CANCER
英文摘要

Epigenetic aberration is known to be important in human carcinogenesis. Promoter methylation status of RAS effector related genes, RASSF1A, RASSF2A, hDAB2IP (m2a and m2b regions) and BLU, was evaluated in 76 endometrial carcinomas and their non-neoplastic endometrial tissue by methylation specific PCR. Hypermethylation of at least one of the 5 genes was detected in 73.7% of carcinomas. There were significant correlations between methylation of hDAB2IP and RASSF1A, RASSF2A (p = 0.042, p = 0.012, respectively). Significantly, more frequent RASSF1A hypermethylation was found in Type I endometrioid carcinomas than Type II carcinomas (p = 0.049). Among endometrioid cancers, significant association between RASSF1A hypermethylation and advanced stage, as well as between methylation of hDAB2IP at m2a region with deep myometrial invasion (p < 0.05) was observed. mRNA expression of RASSF1A, RASSF2A and BLU in endometrial cancer cell lines significantly increased after treatment with the demethylating agent 5-Aza-2′-deoxycytidine supporting the repressive effect of hypermethylation on their transcription. Immunohistochemical study of DNMT1 on eight normal endometrium, 16 hyperplastic endometrium without atypia, 40 atypical complex hyperplasia and 79 endometrial carcinomas showed progressive increase in DNMT1 immunoreactivity from normal endometrium to endometrial hyperplasia and endometrioid carcinomas (p = 0.001). Among carcinomas, distinctly higher DNMT1 expression was observed in Type I endometrioid carcinomas (p < 0.001). DNMT1 immunoreactivity correlated with RASSF1A and RASSF2A methylation (p < 0.05). The data suggested that hypermethylation of RAS related genes, particularly RASSF1A, was involved in endometrial carcinogenesis with possible divergent patterns in different histological types. DNMT1 protein overexpression might contribute to such aberrant DNA hypermethylation of specific tumor suppressor genes in endometrial cancers. (C) 2008 Wiley-Liss, Inc.

语种英语
WOS记录号WOS:000256760300008
引用统计
被引频次:55[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59898
专题北京大学第二临床医学院_病理科
作者单位1.Univ Hong Kong, Queen Mary Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Pathol, Beijing 100871, Peoples R China
3.Univ Hong Kong, Dept Obstet & Gynaecol, Hong Kong, Peoples R China
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GB/T 7714
Liao, Xiaoyun,Siu, Michelle Kwan-Yee,Chan, Kelvin Yuen-Kwong,et al. Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis[J]. INTERNATIONAL JOURNAL OF CANCER,2008,123(2):296-302.
APA Liao, Xiaoyun.,Siu, Michelle Kwan-Yee.,Chan, Kelvin Yuen-Kwong.,Wong, Esther Shuk-Ying.,Ngan, Hextan Yuen-Sheung.,...&Cheung, Annie Nga-Yin.(2008).Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis.INTERNATIONAL JOURNAL OF CANCER,123(2),296-302.
MLA Liao, Xiaoyun,et al."Hypermethylation of RAS effector related genes and DNA methyltransferase 1 expression in endometrial carcinogenesis".INTERNATIONAL JOURNAL OF CANCER 123.2(2008):296-302.
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