Mammary tumor suppression by transforming growth factor beta 1 transgene expression.

Pierce DF, Gorska AE, Chytil A, Meise KS, Page DL, Coffey RJ, Moses HL
Proc Natl Acad Sci U S A. 1995 92 (10): 4254-8

PMID: 7753792 · PMCID: PMC41922 · DOI:10.1073/pnas.92.10.4254

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.

MeSH Terms (22)

9,10-Dimethyl-1,2-benzanthracene Adenocarcinoma Adenoma Aging Animals Crosses, Genetic Enhancer Elements, Genetic Exons Female Globins Male Mammary Glands, Animal Mammary Neoplasms, Experimental Mammary Tumor Virus, Mouse Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Polymerase Chain Reaction Promoter Regions, Genetic Rabbits Transforming Growth Factor beta

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