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Consequences of Epithelial or Stromal TGFβ1 Depletion in the Mammary Gland

  • David H. Nguyen
  • Haydeliz Martinez-Ruiz
  • Mary Helen Barcellos-Hoff
Article

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.

Keywords

TGFβ Carcinogenesis Stromal-epithelial interactions Mammary gland Ionizing radiation 

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

Notes

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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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • David H. Nguyen
    • 1
    • 2
  • Haydeliz Martinez-Ruiz
    • 2
  • Mary Helen Barcellos-Hoff
    • 2
  1. 1.Endocrinology Graduate GroupUniversity of CaliforniaBerkeleyUSA
  2. 2.Departments of Radiation Oncology and Cell BiologyNew York University School of MedicineNew YorkUSA

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