Urethane-induced Mammary Carcinogenesis Susceptibility in Transgenic Mice Expressing a Dominant-negative TGF-β Type II Receptor.

BACKGROUND/AIM: Transforming growth factor-β (TGF-β) plays dual suppressive and oncogenic roles in mammary carcinogenesis. MATERIALS AND METHODS: To analyze whether TGF-β exerts suppressive or oncogenic actions on mammary carcinogenesis, transgenic mice overexpressing a dominant-negative mutant type II TGF-β receptor (TβRII-DNR) driven by the mouse mammary tumor virus (MMTV) promoter were treated with a low dose of urethane, a carcinogen present in fermented food products and alcoholic beverages. RESULTS: Lobular proliferative lesions, showing high β-casein expression, developed in the mammary glands of TβRII-DNR+/+ mice aged >61 weeks. Compared with wild-type mice, TβRII-DNR+/+ mice administered with urethane showed significant increases in dysplastic hyperplasias and adenocarcinomas of the mammary glands. CONCLUSION: The functional decline of TGF-β signaling in mammary glands led to a high susceptibility to urethane-induced mammary carcinogenesis. TGF-β signaling may act as a tumor suppressor during mammary tumor development.