TGF-β Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia

Neil A. Bhowmick, Anna Chytil, David Plieth, Agnieszka E. Gorska, Nancy Dumont, Scott Shappell, M. Kay Washington, Eric G. Neilson, Harold L. Moses*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1090 Scopus citations

Abstract

Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor-β (TGF-β) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-β type II receptor gene in mouse fibroblasts (Tgfbr2fspKO). The loss of TGF-β responsiveness in fibroblasts resulted in intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach, both associated with an increased abundance of stromal cells. Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as one possible mechanism for stimulation of epithelial proliferation. Thus, TGF-β signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues.

Original languageEnglish (US)
Pages (from-to)848-851
Number of pages4
JournalScience
Volume303
Issue number5659
DOIs
StatePublished - Feb 6 2004

ASJC Scopus subject areas

  • General

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