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

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56 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)380-389
Number of pages10
JournalNeoplasia
Volume6
Issue number4
DOIs
StatePublished - Jul 1 2004

Keywords

  • Breast cancer
  • Laser capture microdissection
  • Methylation
  • Tumor suppressor
  • maspin

ASJC Scopus subject areas

  • Cancer Research

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    Futscher, B. W., O'Meara, M. M., Kim, C. J., Rennels, M. A., Lu, D., Gruman, L. M., Seftor, R. E. B., Hendrix, M. J. C., & Domann, F. E. (2004). Aberrant methylation of the maspin promoter is an early event in human breast cancer. Neoplasia, 6(4), 380-389. https://doi.org/10.1593/neo.04115