Loss of GDF-15 abolishes Sulindac chemoprevention in the Apc Min/+ mouse model of intestinal cancer

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Background: Growth-differentiation factor (GDF)-15, a member of the TGF-beta superfamily, is potently induced in the intestine following mechanical injury, genotoxic insult and following non-steroidal anti-inflammatory drugs (NSAIDs) exposure. GDF-15 expression correlates with apoptosis in intestinal cells and has been implicated in the pathogenesis of colorectal cancer formation and the anti-tumor effects of NSAIDs. We sought to determine the effect of loss of Gdf15 on animal tumor models of hereditary colon cancer and in the NSAID-mediated prevention of heritable colorectal cancer. Methods: GDF-15 null (Gdf15 -/-) mice and mice with the genetic mutation found in hereditary poliposis coli, Apc min/+ were bred. Gdf15 -/-, Apc min/+ and Gdf15 +/+, Apc min/+ mice were generated. Results: In Gdf15 -/-, Apc min/+ mice, intestinal neoplasia formation rate and size were indistinguishable from that in Gdf15 +/+, Apc min/+ mice. Sulindac chemoprotection activity although potent in Gdf15 +/+, Apc min/+ mice was abolished in Gdf15 -/-, Apc min/+ mice. Conclusions: These results demonstrate in a murine model that GDF-15 does not significantly regulate heritable in vivo intestinal carcinogenesis but does mediate sulindac chemoprevention in heritable colon cancer. These data suggest that the use of GDF-15 activated signaling pathways may allow improved chemoprevention and therapies for colorectal cancer.

Original languageEnglish (US)
Pages (from-to)571-576
Number of pages6
JournalJournal of Cancer Research and Clinical Oncology
Issue number4
StatePublished - Apr 1 2010
Externally publishedYes


  • COX-2
  • Colon cancer
  • Cytokine
  • TGF-beta

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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