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学科主题: 临床医学
题名:
Epigenetic and genetic alterations of p33(ING1b) in ovarian cancer
作者: Shen, DH; Chan, KYK; Khoo, US; Ngan, HYS; Xue, WC; Chiu, PM; Ip, P; Cheung, ANY
刊名: CARCINOGENESIS
发表日期: 2005-04-01
DOI: 10.1093/carcin/bgi011
卷: 26, 期:4, 页:855-863
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]: TUMOR-SUPPRESSOR P33(ING1) ; DNA METHYLATION ; REDUCED EXPRESSION ; DOWN-REGULATION ; P53 EXPRESSION ; MELANOMA-CELLS ; BREAST-CANCER ; MESSENGER-RNA ; ING1 ; INHIBITOR
英文摘要:

p33(ING1b) is a candidate tumor suppressor gene and a nuclear protein. We investigated whether genetic and epigenetic mechanisms affect p33(ING1b) expression in ovarian cancer thus contributing toward its pathogenesis. A total of 111 ovarian cancers collected from Beijing and Hong Kong were used for this study. Weak or negative p33(ING1b) protein expression was demonstrated by immunohistochemistry on tissue microarray in 28/111 cases. Real-time quantitative RT-PCR also showed overall significant reduction of p33(ING1b) mRNA expression (P = 0.0137), with 53.1% (17/32) cases showing 2- to 5-fold reduction and absence of expression. The reduction of mRNA expression in cancer correlated with decreased p33(ING1b) protein expression (P < 0.0001). While no p33(ING1b) mutation was found, allelic loss at the p33(ING1b) locus was demonstrated in 25% (8/32) cases. The allelic loss profiles also showed statistical significant correlation with reduction of p33(ING1b) protein and mRNA expression (P = 0.031 and 0.030). Promoter methylation as assessed by methylation specific PCR was found in 23.9% (21/88) cases analyzed. Bisulfite sequencing results confirmed the p33(ING1b) promoter methylation status of these methylation positive cases. Statistical significant correlation between methylation and mRNA expression (P = 0.006) was demonstrated. Treatment with demethylating drug, 5′-aza-2′-deoxycytidine, resulted in dosage-dependent elevated mRNA expression of p33(ING1b) in ovarian cancer cell lines. This is the first study reporting epigenetic mechanism regulating the p33(ING1b) expression. Our findings support that genetic and epigenetic alteration of p33(ING1b) are likely to contribute towards the pathogenesis of ovarian cancers.

语种: 英语
WOS记录号: WOS:000227976700018
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/68082
Appears in Collections:北京大学第二临床医学院_病理科_期刊论文

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作者单位: 1.Univ Hong Kong, Hong Kong Jockey Club Clin Res Ctr, Dept Obstet & Gynecol, Hong Kong, Hong Kong, Peoples R China
2.Univ Hong Kong, Dept Pathol, SH Ho Fdn, Res Labs Pathol, Hong Kong, Hong Kong, Peoples R China
3.Peking Univ, Peoples Hosp, Dept Pathol, Beijing 100871, Peoples R China

Recommended Citation:
Shen, DH,Chan, KYK,Khoo, US,et al. Epigenetic and genetic alterations of p33(ING1b) in ovarian cancer[J]. CARCINOGENESIS,2005,26(4):855-863.
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