Mammary gland involution provides a unique model to study the TGF-β cancer paradox

Qiuchen Guo, Courtney Betts, Nathan Pennock, Elizabeth Mitchell, Pepper Schedin

Research output: Contribution to journalReview articlepeer-review

21 Scopus citations


Transforming Growth Factor-β (TGF-β) signaling in cancer has been termed the “TGF-β paradox”, acting as both a tumor suppresser and promoter. The complexity of TGF-β signaling within the tumor is context dependent, and greatly impacted by cellular crosstalk between TGF-β responsive cells in the microenvironment including adjacent epithelial, endothelial, mesenchymal, and hematopoietic cells. Here we utilize normal, weaning-induced mammary gland involution as a tissue microenvironment model to study the complexity of TGF-β function. This article reviews facets of mammary gland involution that are TGF-β regulated, namely mammary epithelial cell death, immune activation, and extracellular matrix remodeling. We outline how distinct cellular responses and crosstalk between cell types during physiologically normal mammary gland involution contribute to simultaneous tumor suppressive and promotional microenvironments. We also highlight alternatives to direct TGF-β blocking anti-cancer therapies with an emphasis on eliciting concerted microenvironmental-mediated tumor suppression.

Original languageEnglish (US)
JournalJournal of Clinical Medicine
Issue number1
StatePublished - Jan 1 2017


  • Cancer
  • Cellular crosstalk
  • TGF-β
  • Weaning-induced mammary gland involution

ASJC Scopus subject areas

  • Medicine(all)


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