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CpG island shore methylation regulates caveolin-1 expression in breast cancer

Authors
Rao, XEvans, JChae, HPilrose, JKim, SYan, PHuang, RLLai, HCLin, HLiu, YMiller, DRhee, JKHuang, YWGu, FGray, JWHuang, THMNephew, KP
Issue Date
Sep-2013
Publisher
NATURE PUBLISHING GROUP
Keywords
breast cancer; Cav1; CpG island shore; DNA methylation
Citation
ONCOGENE, v.32, no.38, pp 4519 - 4528
Pages
10
Journal Title
ONCOGENE
Volume
32
Number
38
Start Page
4519
End Page
4528
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/147537
DOI
10.1038/onc.2012.474
ISSN
0950-9232
1476-5594
Abstract
Caveolin-1 (Cav1) is an integral membrane, scaffolding protein found in plasma membrane invaginations (caveolae). Cav1 regulates multiple cancer-associated processes. In breast cancer, a tumor suppressive role for Cav1 has been suggested; however, Cav1 is frequently overexpressed in aggressive breast cancer subtypes, suggesting an oncogenic function in advanced-stage disease. To further delineate Cav1 function in breast cancer progression, we evaluated its expression levels among a panel of cell lines representing a spectrum of breast cancer phenotypes. In basal-like (the most aggressive BC subtype) breast cancer cells, Cav1 was consistently upregulated, and positively correlated with increased cell proliferation, anchorage-independent growth, and migration and invasion. To identify mechanisms of Cav1 gene regulation, we compared DNA methylation levels within promoter 'CpG islands' (CGIs) with 'CGI shores', recently described regions that flank CGIs with less CG-density. Integration of genome-wide DNA methylation profiles ('methylomes') with Cav1 expression in 30 breast cancer cell lines showed that differential methylation of CGI shores, but not CGIs, significantly regulated Cav1 expression. In breast cancer cell lines having low Cav1 expression (despite promoter CGI hypomethylation), we found that treatment wi
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공과대학 (소프트웨어학부(첨단))
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