Open AccessMammary tumor suppression by transforming growth factor beta 1 transgene expression.
Author(s) -
Donald F. Pierce,
Agnieszka E. Gorska,
Anna Chytil,
Katherine S. Meise,
David L. Page,
Robert J. Coffey,
Harold L. Moses
Publication year - 1995
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.92.10.4254
Subject(s) - mammary tumor , mouse mammary tumor virus , transgene , mammary gland , biology , transforming growth factor , tgf alpha , genetically modified mouse , transforming growth factor beta , cancer research , endocrinology , medicine , cell culture , epidermal growth factor , cancer , immunology , gene , virus , biochemistry , genetics , breast cancer
In cell culture, type alpha transforming growth factor (TGF-alpha) stimulates epithelial cell growth, whereas TGF-beta 1 overrides this stimulatory effect and is growth inhibitory. Transgenic mice that overexpress TGF-alpha under control of the mouse mammary tumor virus (MMTV) promoter/enhancer exhibit mammary ductal hyperplasia and stochastic development of mammary carcinomas, a process that can be accelerated by administration of the chemical carcinogen 7,12-dimethylbenz[a]anthracene. MMTV-TGF-beta 1 transgenic mice display mammary ductal hypoplasia and do not develop mammary tumors. We report that in crossbreeding experiments involving the production of mice carrying both the MMTV-TGF-beta 1 and MMTV-TGF-alpha transgenes, there is marked suppression of mammary tumor formation and that MMTV-TGF-beta 1 transgenic mice are resistant to 7,12-dimethylbenz[a]anthracene-induced mammary tumor formation. These data demonstrate that overexpression of TGF-beta 1 in vivo can markedly suppress mammary tumor development.