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Consequences of Epithelial or Stromal TGFβ1 Depletion in the Mammary Gland

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.

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Abbreviations

TGFβ:

Transforming growth factor β1

LAP:

Latency associated peptide

LTBP:

Latent TGFβ binding proteins

LTGFβ:

Latent TGFβ

ER:

Estrogen receptor

PR:

Progesterone receptor

ROS:

Reactive oxygen species

ATM:

Ataxia telangiectasia mutated

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Acknowledgements

The authors wish to acknowledge funding from the Bay Area Breast Cancer and the Environment Research Center grant number U01 ES012801 from the National Institute of Environmental Health Sciences, NIH and the National Cancer Institute, NIH and from the Department of Energy OBER Low Dose Radiation Program. DHN is recipient of a pre-doctoral fellowship from the DOD-Breast Cancer Research Program.

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Correspondence to Mary Helen Barcellos-Hoff.

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Nguyen, D.H., Martinez-Ruiz, H. & Barcellos-Hoff, M.H. Consequences of Epithelial or Stromal TGFβ1 Depletion in the Mammary Gland. J Mammary Gland Biol Neoplasia 16, 147–155 (2011). https://doi.org/10.1007/s10911-011-9218-0

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Keywords

  • TGFβ
  • Carcinogenesis
  • Stromal-epithelial interactions
  • Mammary gland
  • Ionizing radiation