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Aberrant Methylation of the Maspin Promoter Is an Early Event in Human Breast Cancer1
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...
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Published in: | Neoplasia (New York, N.Y.) N.Y.), 2004-07, Vol.6 (4), p.380-389 |
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Main Authors: | , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 1522-8002 1476-5586 |