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胶原蛋白和钙结合表皮生长因子结构域 1 常因启动子异常甲基化失活，调节细胞迁移和存活。

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

机构信息

Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW 2010, Australia.

出版信息

Br J Cancer. 2010 Jan 5;102(1):87-96. doi: 10.1038/sj.bjc.6605429. Epub 2009 Nov 24.

DOI:10.1038/sj.bjc.6605429
PMID:19935792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2813742/
Abstract

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.

摘要

背景

胶原蛋白和钙结合表皮生长因子域 1（CCBE1）是一个尚未被阐明的基因，在乳腺癌中表达下调。由于 CCBE1 定位于 18q21.32，这是卵巢癌中经常出现杂合性丢失的区域，因此本研究旨在确定 CCBE1 在卵巢癌中的表达和功能。

方法

在卵巢癌细胞系和原发性肿瘤中确定 CCBE1 的表达和甲基化模式。CCBE1 含有胶原蛋白重复序列和天冬氨酸/天冬酰胺羟化/表皮生长因子样结构域，表明其在细胞外基质重塑和迁移中具有功能，这通过细胞系中的小干扰 RNA（siRNA）介导的敲低和 CCBE1 的过表达来确定。

结果

CCBE1 在正常卵巢中表达，但在卵巢癌细胞系和原发性癌中减少。卵巢癌细胞系中的药物去甲基化/去乙酰化重新诱导了 CCBE1 的表达，表明表观遗传机制有助于其在癌症中的沉默。在 11 个卵巢癌细胞系中的 6 个（55%）和 81 个卵巢癌中的 38 个（41%）检测到 CCBE1 启动子甲基化。在卵巢癌细胞系中，通过 siRNA 介导的 CCBE1 敲低增强了其迁移；相反，CCBE1 的重新表达降低了迁移和存活。因此，CCBE1 表达的缺失可能通过增强迁移和细胞存活来促进卵巢癌的发生。

结论

这些数据表明 CCBE1 是卵巢癌中的一个新的候选肿瘤抑制因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/fe26fd119fcf/6605429f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/3a342d036a0b/6605429f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/4ccddf5b203b/6605429f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/cdd2fc2bc703/6605429f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/fe26fd119fcf/6605429f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/3a342d036a0b/6605429f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/4ccddf5b203b/6605429f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/cdd2fc2bc703/6605429f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a659/2813742/fe26fd119fcf/6605429f4.jpg

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