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Transforming growth factor beta receptor type II inactivation promotes the establishment and progression of colon

Swati Biswas1, Anna Chytil, Kay Washington

  • 1Department of Medicine, Vanderbilt University Medical School, Nashville, TN, USA.

Cancer Research
|July 17, 2004
PubMed

Insights

Loss of TGF-beta receptor type II (TGFBR2) in colon cells promotes colon cancer. This study shows TGFBR2 inactivation drives tumor growth in a mouse model, confirming its role as a colon tumor suppressor.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Transforming growth factor-beta (TGF-beta) signaling pathway deregulation is common in colon cancers.
  • Mutational inactivation of TGF-beta receptor type II (TGFBR2) is the most frequent genetic event, occurring in 20-30% of colon cancers.

Purpose of the Study:

  • To investigate the in vivo effect of TGF-beta signaling loss on colon cancer formation.
  • To generate and utilize a mouse model null for Tgfbr2 in the colonic epithelium.

Main Methods:

  • Generated a mouse model by mating Fabpl(4xat-132) Cre mice with Tgfbr2(flx/flx) mice, creating a colonic epithelium Tgfbr2 null model.
  • Administered azoxymethane (AOM) to induce colon cancer in the generated mouse model and control groups.
  • Assessed tumor incidence, multiplicity, and proliferation in neoplasms.

Main Results:

  • Fabpl(4xat-132) Cre Tgfbr2(flx/flx) mice exhibited a significant increase in AOM-induced adenomas and adenocarcinomas compared to controls.
  • Increased proliferation was observed in neoplasms within the Tgfbr2-deficient colon epithelial cells.
  • Loss of TGF-beta-mediated growth inhibition is implicated as a mechanism contributing to colon cancer formation.

Conclusions:

  • Loss of TGFBR2 in colon epithelial cells promotes the establishment and progression of AOM-induced colon neoplasms.
  • This study provides in vivo evidence that TGFBR2 functions as a tumor suppressor gene in the colon.

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