Maspin expression inversely correlates with breast tumor progression in MMTV/TGF-alpha transgenic mouse model

K. B. Reddy, R. McGowen, L. Schuger, D. Visscher, S. Sheng

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Maspin is a novel serine protease inhibitor (serpin) with tumor suppressive activity. To date, despite the mounting evidence implicating the potential diagnostic/prognostic and therapeutic value of maspin in breast and prostate carcinoma, the lack of a suitable animal model hampers the in vivo investigation on the role of maspin at different stages of tumor progression. In this study, we used MMTV/TGF-α transgenic mouse model to study the expression profile of maspin in mammary tumor progression. Histopathological examinations of MMTV/TGF-α transgenic mice revealed TGF-α expression leading to hyperproliferation, hyperplasia, and occasional carcinoma in mammary gland. Interestingly, when MMTV/TGF-α transgenic mice were breed to homozygocity, they also developed characteristic skin papillomas. Immunohistochemistry analysis of maspin expression in the breast tissues of TGF-α transgenic mice showed a direct correlation between down-regulation of maspin expression and tumor progression. The loss of maspin expression was concomitant with the critical transition from carcinoma in situ to invasive carcinoma. Subsequent in-situ hybridization analyses suggest that the down-regulation of maspin expression is primarily a transcriptional event. This data is consistent with the tumor suppressive role of maspin. Furthermore, our data suggests that MMTV/TGF-α transgenic mouse model is advantageous for in vivo evaluation of both the expression and the biological function of maspin during the slow multi-stage carcinogenesis of mammary gland.

Original languageEnglish (US)
Pages (from-to)6538-6543
Number of pages6
JournalOncogene
Volume20
Issue number45
DOIs
StatePublished - Oct 4 2001

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Keywords

  • Carcinoma in situ
  • Hyperplasia
  • Immunohistochemistry
  • In situ hybridization
  • Invasive carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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