Aberrant methylation of the maspin promoter is an early event in human breast cancer

Bernard W Futscher; Megan M O'Meara; Christina J Kim; Margaret A Rennels; Di Lu; Lynn M Gruman; Richard E B Seftor; Mary J C Hendrix; Frederick E Domann

doi:10.1593/neo.04115

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Aberrant methylation of the maspin promoter is an early event in human breast cancer

Journal article

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Aberrant methylation of the maspin promoter is an early event in human breast cancer

Bernard W Futscher, Megan M O'Meara, Christina J Kim, Margaret A Rennels, Di Lu, Lynn M Gruman, Richard E B Seftor, Mary J C Hendrix and Frederick E Domann

Neoplasia (New York, N.Y.), Vol.6(4), pp.380-389

07/2004

DOI: 10.1593/neo.04115

PMCID: PMC1502109

PMID: 15256060

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Abstract

The maspin gene functions as a tumor suppressor in human breasts, and its expression is frequently lost during breast cancer progression. In vitro models of human breast cancer indicate that the loss of maspin expression is closely linked to aberrant methylation of the maspin promoter. We conducted a study on 30 archival ductal carcinoma in situ (DCIS) specimens to determine if aberrant methylation of the maspin promoter occurred in vivo, and whether it occurred early in breast cancer evolution. Healthy tissue obtained from reduction mammoplasty was used as normal control. Results from immunohistochemical analysis indicate that maspin expression is lost in a substantial fraction of DCIS specimens (57%). Bisulfite sequencing of DNA isolated from laser capture-microdissected normal and neoplastic ducts showed that loss of maspin expression was often, but not always, linked to aberrant methylation of the maspin promoter, suggesting that other mechanisms, in addition to aberrant methylation, participate and/or cooperate to silence maspin gene expression. Taken together, these results indicate that aberrant methylation of the maspin promoter is an early event in human breast cancer.

Serpins - genetics

Carcinoma in Situ - pathology

Carcinoma, Ductal - genetics

Carcinoma, Ductal - pathology

Humans

DNA Primers

Promoter Regions, Genetic - genetics

Proteins - genetics

DNA Methylation

Breast Neoplasms - genetics

Carcinoma in Situ - genetics

Breast Neoplasms - pathology

Base Sequence

Female

Genes, Tumor Suppressor

Details

Title: Subtitle: Aberrant methylation of the maspin promoter is an early event in human breast cancer
Creators: Bernard W Futscher - Bone Marrow Transplant Program, Arizona Cancer Center, and Department of Pharmacology and Toxicology, The University of Arizona, Tucson, AZ 85724, USA. bfutscher@azcc.arizona.edu
Megan M O'Meara
Christina J Kim
Margaret A Rennels
Di Lu
Lynn M Gruman
Richard E B Seftor
Mary J C Hendrix
Frederick E Domann
Resource Type: Journal article
Publication Details: Neoplasia (New York, N.Y.), Vol.6(4), pp.380-389
Publisher: United States
DOI: 10.1593/neo.04115
PMID: 15256060
PMCID: PMC1502109
ISSN: 1522-8002
eISSN: 1476-5586
Grant note: ES06694 / NIEHS NIH HHS R29 CA073612 / NCI NIH HHS CA65562 / NCI NIH HHS CA75681 / NCI NIH HHS R01 CA075681 / NCI NIH HHS P30 ES006694 / NIEHS NIH HHS P01 CA066081 / NCI NIH HHS R56 CA073612 / NCI NIH HHS CA73612 / NCI NIH HHS CA66081 / NCI NIH HHS R01 CA073612 / NCI NIH HHS
Language: English
Date published: 07/2004
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984047607702771

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