DNA methylation-dependent silencing of CST6 in human breast cancer cell lines.

DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Research Abstract Details 

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DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Abstract Text:

Ashley G Rivenbark,Wendell D Jones,William B Coleman,

Cystatin M (CST6) is a candidate breast cancer tumor suppressor that is expressed in normal and premalignant breast epithelium, but not in metastatic breast cancer cell lines. CST6 is subject to epigenetic silencing in MCF-7 breast cancer cells related to methylation of the CpG island that encompasses the CST6 proximal promoter region and exon 1. In the current study, CST6 CpG island methylation and expression status was examined in a panel of breast cancer cell lines. Seven of 12 (58%) cell lines lack detectable expression of CST6 and treatment of these cells with 5-aza-2'-deoxycytidine resulted in a significant increase in CST6 expression, suggesting that the loss of expression may be related to methylation-dependent epigenetic silencing. Bisulfite sequencing of CST6 in a subset of breast cancer cell lines revealed CpG island hypermethylation in CST6-negative cells, and an absence of CpG island methylation in cells that express CST6. The extent of regional methylation was strongly associated with the lack of expression of CST6 among these cell lines. In particular, hypermethylation of the proximal promoter was significantly associated with CST6 gene silencing, and methylation of a number of individual CpGs was found to be statistically correlated with extinction of gene expression. These results establish a strong link between CST6 promoter hypermethylation and loss of CST6 expression in breast cancer cell lines, and suggest that methylation-dependent epigenetic silencing of CST6 may represent an important mechanism for loss of CST6 during breast carcinogenesis in vivo.

DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Publishing Authors By Initials

AG Rivenbark,WD Jones,WB Coleman,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: base sequence: regulatory sequences, nucleic acid: promoter regions (genetics) research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: molecular structure: base sequence: regulatory sequences, nucleic acid: promoter regions (genetics) research

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DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Laboratory investigation; a journal of technical m

VOLUME: 86

Page Numbers: 1233-42

Journal Abbreviation: Lab. Invest.

ISSN: 0023-6837

DAY: 16

MONTH: 10

YEAR: 2006

DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376617

DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Keywords Mesh Terms:

KEYWORDS: Promoter Regions (Genetics)

MESH TERMS: physiology

Chemical & Substance for Abstract: DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. Information

Substance Name: Azacitidine

Registry Number: 320-67-2

Grant and Affiliation Information for DNA methylation-dependent silencing of CST6 in human breast cancer cell lines.

AFFILIATION: Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA78343

ACRONYM: CA

MEDLINETA: Lab Invest

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