Breast Cancer Research

official impact factor 5.79

Review

Transforming growth factor-beta and breast cancer: Lessons learned from genetically altered mouse models

Lalage M Wakefield, Yu-an Yang and Oksana Dukhanina

Author Affiliations

National Cancer Institute, Bethesda, Maryland, USA

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Breast Cancer Res 2000, 2:100-106 doi:10.1186/bcr41

Published: 21 February 2000

Abstract

Transforming growth factor (TGF)-βs are plausible candidate tumor suppressors in the breast. They also have oncogenic activities under certain circumstances, however. Genetically altered mouse models provide powerful tools to analyze the complexities of TGF-βaction in the context of the whole animal. Overexpression of TGF-β can suppress tumorigenesis in the mammary gland, raising the possibility that use of pharmacologic agents to enhance TGF-β function locally might be an effective method for the chemoprevention of breast cancer. Conversely, loss of TGF-β response increases spontaneous and induced tumorigenesis in the mammary gland. This confirms that endogenous TGF-βs have tumor suppressor activity in the mammary gland, and suggests that the loss of TGF-β receptors seen in some human breast hyperplasias may play a causal role in tumor development.

Keywords:
dominant-negative mutant receptors; mammary gland; transforming growth factor-β; transgenic mice; tumor suppressor