Consequences of epithelial or stromal TGFβ1 depletion in the mammary gland

J Mammary Gland Biol Neoplasia. 2011 Jun;16(2):147-55. doi: 10.1007/s10911-011-9218-0. Epub 2011 May 17.

Abstract

Transforming growth factor β1 (TGFβ) affects stroma and epithelial composition and interactions that mediate mammary development and determine the course of cancer. The reduction of TGFβ in Tgfβ1 heterozygote mice, which are healthy and long-lived, provides an important model to dissect the contribution of TGFβ in mammary gland biology and cancer. We used both intact mice and mammary chimeras in conjunction with Tgfβ1 genetic depletion and TGFβ neutralizing antibodies to evaluate how stromal or epithelial TGFβ depletion affect mammary development and response to physiological stimuli. Our studies of radiation carcinogenesis have revealed new aspects of TGFβ biology and suggest that the paradoxical TGFβ switch from tumor suppressor to tumor promoter can be resolved by assessing distinct stromal versus epithelial actions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Female
  • Humans
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mammary Glands, Human / cytology*
  • Mammary Glands, Human / metabolism*
  • Mammary Glands, Human / pathology
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Stromal Cells / metabolism*
  • Stromal Cells / pathology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • Transforming Growth Factor beta1