The loss of TGF-β signaling promotes prostate cancer metastasis

William H. Tu, Tania Z. Thomas, Naoya Masumori, Neil A. Bhowmick, Agnieszka E. Gorska, Yu Shyr, Susan Kasper, Tom Case, Richard L. Roberts, Scott B. Shappell, Harold L. Moses, Robert J. Matusik

Research output: Contribution to journalArticlepeer-review

86 Citations (Scopus)

Abstract

In breast and colon cancers, transforming growth factor (TGF)-β signaling initially has an antineoplastic effect, inhibiting tumor growth, but eventually exerts a proneoplastic effect, increasing motility and cancer spread. In prostate cancer, studies using human samples have correlated the loss of the TGF-β type II receptor (TβRII) with higher tumor grade. To determine the effect of an inhibited TGF-β pathway on prostate cancer, we bred transgenic mice expressing the tumorigenic SV40 large T antigen in the prostate with transgenic mice expressing a dominant negative TβRII mutant (DNIIR) in the prostate. Transgene(s) and TGF-β1 expression were identified in the prostate and decreased protein levels of plasminogen activator inhibitor type I, as a marker for TGF-β signaling, correlated with expression of the DNIIR. Although the sizes of the neoplastic prostates were not enlarged, increased amounts of metastasis were observed in mice expressing both transgenes compared to age-matched control mice expressing only the large T antigen transgene. Our study demonstrates for the first time that a disruption of TGF-β signaling in prostate cancer plays a causal role in promoting tumor metastasis.

Original languageEnglish
Pages (from-to)267-277
Number of pages11
JournalNeoplasia
Volume5
Issue number3
DOIs
Publication statusPublished - 2003

All Science Journal Classification (ASJC) codes

  • Cancer Research

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