TGF-β Biology in Mammary Development and Breast Cancer

  1. Mary Helen Barcellos-Hoff2
  1. 1Department of Cancer Biology and Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232
  2. 2Department of Radiation Oncology and Department of Cell Biology, New York University School of Medicine, New York, New York 10016
  1. Correspondence: mhbarcellos-hoff{at}nyumc.org

Abstract

Transforming growth factor-β1 (TGF-β) was first implicated in mammary epithelial development by Daniel and Silberstein in 1987 and in breast cancer cells and hormone resistance by Lippman and colleagues in 1988. TGF-β is critically important for mammary morphogenesis and secretory function through specific regulation of epithelial proliferation, apoptosis, and extracellular matrix. Differential TGF-β effects on distinct cell types are compounded by regulation at multiple levels and the influence of context on cellular responses. Studies using controlled expression and conditional-deletion mouse models underscore the complexity of TGF-β biology across the cycle of mammary development and differentiation. Early loss of TGF-β growth regulation in breast cancer evolves into fundamental deregulation that mediates cell interactions and phenotypes driving invasive disease. Two outstanding issues are to understand the mechanisms of biological control in situ and the circumstances by which TGF-β regulation is subverted in neoplastic progression.

Footnotes

  • Editors: Mina J. Bissell, Kornelia Polyak, and Jeffrey Rosen

  • Additional Perspectives on The Mammary Gland as an Experimental Model available at www.cshperspectives.org



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      1. Cold Spring Harb. Perspect. Biol. 3: a003277 Copyright © 2011 Cold Spring Harbor Laboratory Press; all rights reserved

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