Urethane-induced mammary carcinogenesis susceptibility in transgenic mice expressing a dominant-negative tgf-β type II receptor

Abstract

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 (TβRIIDNR) 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 wildtype 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.