Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis

Reginald Hill, Yurong Song, Robert Cardiff, Terry Van Dyke

Research output: Contribution to journalArticlepeer-review

269 Scopus citations


Our understanding of cancer has largely come from the analysis of aberrations within the tumor cell population. Yet it is increasingly clear that the tumor microenvironment can significantly influence tumorigenesis. For example, the mesenchyme can support the growth of tumorigenic epithelium. However, whether fibroblasts are subject to genetic/epigenetic changes as a result of selective pressures conferred by oncogenic stress in the epithelium has not been experimentally assessed. Recent analyses of some human carcinomas have shown tumor-suppressor gene mutations within the stroma, suggesting that the interplay among multiple cell types can select for aberrations nonautonomously during tumor progression. We demonstrate that this indeed occurs in a mouse model of prostate cancer where epithelial cell cycle disruption via cell-specific inhibition of pRb function induces a paracrine p53 response that suppresses fibroblast proliferation in associated stroma. This interaction imposes strong selective pressure yielding a highly proliferative mesenchyme that has undergone p53 loss.

Original languageEnglish (US)
Pages (from-to)1001-1011
Number of pages11
Issue number6
StatePublished - Dec 16 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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