Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression.

Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Research Abstract Details 

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Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Abstract Text:

Lingbao Ai,Wan-Ju Kim,Tae-You Kim,C Robert Fields,Nicole A Massoll,Keith D Robertson,Kevin D Brown,

Cystatin M is a secreted inhibitor of lysosomal cysteine proteases. Several lines of evidence indicate that cystatin M is a tumor suppressor important in breast malignancy; however, the mechanism(s) that leads to inactivation of cystatin M during cancer progression is unknown. Inspection of the human cystatin M locus uncovered a large and dense CpG island within the 5' region of this gene (termed CST6). Analysis of cultured human breast tumor lines indicated that cystatin M expression is either undetectable or in low abundance in several lines; however, enhanced gene expression was measured in cells cultured on the DNA demethylating agent 5-aza-2'-deoxycytidine (5-aza-dC). Increased cystatin M expression does not correlate with a cytotoxic response to 5-aza-dC; rather, various molecular approaches indicated that the CST6 gene was aberrantly methylated in these tumor lines as well as in primary breast tumors. Moreover, 60% (12 of 20) of primary tumors analyzed displayed CST6 hypermethylation, indicating that this aberrant characteristic is common in breast malignancies. Finally, preinvasive and invasive breast tumor cells were microdissected from nine archival breast cancer specimens. Of the five tumors displaying CST6 gene methylation, four tumors displayed methylation in both ductal carcinoma in situ and invasive breast carcinoma lesions and reduced expression of cystatin M in these tumors was confirmed by immunohistochemistry. In summary, this study establishes that the tumor suppressor cystatin M is a novel target for epigenetic silencing during mammary tumorigenesis and that this aberrant event can occur before development of invasive breast cancer.

Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Publishing Authors By Initials

L Ai,WJ Kim,TY Kim,CR Fields,NA Massoll,KD Robertson,KD Brown,

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Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cancer research

VOLUME: 66

Page Numbers: 7899-909

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ISSN: 1538-7445

DAY: 15

MONTH: Aug

YEAR: 2006

Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Epigenetic silencing of the tumor suppressor cystatin M occurs during breast cancer progression.

AFFILIATION: Department of Biochemistry and Molecular Biology and University of Florida Shands Cancer Center Program in Cancer Genetics, Epigenetics, and Tumor Virology, University of Florida College of Medicine, Gainesville, FL 32610, USA.

Country: United States

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MEDLINETA: Cancer Res

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