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

Oncogene. 2001 Oct 4;20(45):6538-43. doi: 10.1038/sj.onc.1204796.


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-alpha transgenic mouse model to study the expression profile of maspin in mammary tumor progression. Histopathological examinations of MMTV/TGF-alpha transgenic mice revealed TGF-alpha expression leading to hyperproliferation, hyperplasia, and occasional carcinoma in mammary gland. Interestingly, when MMTV/TGF-alpha transgenic mice were breed to homozygocity, they also developed characteristic skin papillomas. Immunohistochemistry analysis of maspin expression in the breast tissues of TGF-alpha 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-alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism*
  • Carcinoma in Situ / pathology
  • Disease Progression
  • Down-Regulation*
  • Female
  • Genes, Tumor Suppressor
  • Hyperplasia / genetics
  • Hyperplasia / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Mammary Glands, Animal / metabolism
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Tumor Virus, Mouse / genetics*
  • Mice
  • Mice, Transgenic
  • Neoplasm Invasiveness
  • Protein Biosynthesis*
  • Proteins / genetics
  • Proteins / immunology
  • RNA, Neoplasm / biosynthesis
  • Serpins / biosynthesis*
  • Serpins / genetics
  • Serpins / immunology
  • Transcription, Genetic
  • Transforming Growth Factor alpha / genetics*


  • Proteins
  • RNA, Neoplasm
  • Serpins
  • Transforming Growth Factor alpha