Mammary Tumor Suppression by Transforming Growth Factor β1 Transgene Expression

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 10; pp. 4254 - 4258
• Main Authors: Pierce, Donald F., Gorska, Agnieszka E., Chytil, Anna, Meise, Katherine S., Page, David L., Coffey, Robert J., Moses, Harold L.
• Format: Journal Article
• Language: English
• Published: National Academy of Sciences of the United States of America 09.05.1995
• Subjects: Adenocarcinoma; Animals; Cell growth; Epithelial cells; Female animals; Mammary glands; Mice; Transgenes; Transgenic animals; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.10.4254

In cell culture, type α transforming growth factor (TGF-α) stimulates epithelial cell growth, whereas TGF-β1 overrides this stimulatory effect and is growth inhibitory. Transgenic mice that overexpress TGF-α 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-β1 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-β1 and MMTV-TGF-α transgenes, there is marked suppression of mammary tumor formation and that MMTV-TGF-β1 transgenic mice are resistant to 7,12-dimethylbenz[c]anthracene-induced mammary tumor formation. These data demonstrate that overexpression of TGF-β1 in vivo can markedly suppress mammary tumor development.