Collagen and calcium-binding EGF domains 1 is frequently inactivated in ovarian cancer by aberrant promoter hypermethylation and modulates cell migration and survival

被引：37

作者：

Barton, C. A. ^{[1
]}

Gloss, B. S. ^{[1
]}

Qu, W. ^{[1
]}

Statham, A. L. ^{[1
]}

Hacker, N. F. ^{[1
,2
,3
]}

Sutherland, R. L. ^{[1
,3
]}

Clark, S. J. ^{[1
,3
]}

O'Brien, P. M. ^{[1
,3
]}

机构：

[1] St Vincents Hosp, Garvan Inst Med Res, Canc Res Program, Darlinghurst, NSW 2010, Australia

[2] Royal Hosp Women, Gynaecol Canc Ctr, Randwick, NSW 2031, Australia

[3] Univ NSW, Fac Med, Sydney, NSW 2031, Australia

来源：

BRITISH JOURNAL OF CANCER | 2010年 / 102卷 / 01期

基金：

英国医学研究理事会;

关键词：

ovarian cancer; CCBE1; tumour suppressor; ASPARAGINYL-BETA-HYDROXYLASE; COMPARATIVE GENOMIC HYBRIDIZATION; GROWTH-FACTOR; GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA; VITELLOGENIN RECEPTOR; DNA METHYLATION; OVEREXPRESSION; CHOLANGIOCARCINOMA; ASSOCIATION;

D O I：

10.1038/sj.bjc.6605429

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

BACKGROUND: Collagen and calcium-binding EGF domains 1 (CCBE1) is an uncharacterised gene that has down-regulated expression in breast cancer. As CCBE1 maps to 18q21.32, a region frequently exhibiting loss of heterozygosity in ovarian cancer, the aim of this study was to determine the expression and function of CCBE1 in ovarian cancer. METHODS: Expression and methylation patterns of CCBE1 were determined in ovarian cancer cell lines and primary tumours. CCBE1 contains collagen repeats and an aspartic acid/asparagine hydroxylation/EGF-like domain, suggesting a function in extracellular matrix remodelling and migration, which was determined using small-interfering RNA (siRNA)-mediated knockdown and over-expression of CCBE1 in cell lines. RESULTS: CCBE1 is expressed in normal ovary, but is reduced in ovarian cancer cell lines and primary carcinomas. Pharmacological demethylation/deacetylation in ovarian cancer cell lines re-induced CCBE1 expression, indicating that epigenetic mechanisms contribute to its silencing in cancer. CCBE1 promoter hypermethylation was detected in 6/11 (55%) ovarian cancer cell lines and 38/81 (41%) ovarian carcinomas. siRNA-mediated knockdown of CCBE1 in ovarian cancer cell lines enhanced their migration; conversely, re-expression of CCBE1 reduced migration and survival. Hence, loss of CCBE1 expression may promote ovarian carcinogenesis by enhancing migration and cell survival. CONCLUSIONS: These data suggest that CCBE1 is a new candidate tumour suppressor in ovarian cancer. British Journal of Cancer (2010) 102, 87-96. doi:10.1038/sj.bjc.6605429 www.bjcancer.com Published online 24 November 2009 (C) 2010 Cancer Research UK

引用

页码：87 / 96

页数：10

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