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

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.

journal_name

Neoplasia

authors

Futscher BW,O'Meara MM,Kim CJ,Rennels MA,Lu D,Gruman LM,Seftor RE,Hendrix MJ,Domann FE

doi

10.1593/neo.04115

keywords:

subject

Has Abstract

pub_date

2004-07-01 00:00:00

pages

380-9

issue

4

eissn

1522-8002

issn

1476-5586

journal_volume

6

pub_type

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