Collagen and calcium-binding EGF domains 1 is frequently inactivated in ovarian cancer by aberrant promoter hypermethylation and modulates cell migration and survival
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.
|Authors||Barton, C.A., Gloss, B.S., Qu, W., Statham, A.L., Hacker, N.F., Sutherland, R.L., Clark, S.J.; O'Brien, P.M.|
|Publisher Name||BRITISH JOURNAL OF CANCER|
|URL link to publisher's version||http://www.nature.com/bjc/journal/v102/n1/abs/6605429a.html|
|OpenAccess link to author's accepted manuscript version||https://publications.gimr.garvan.org.au/open-access/10215|