Tgfbr1 haploinsufficiency inhibits the development of murine mutant Kras-induced pancreatic precancer

Kevin Adrian, Matthew J. Strouch, Qinghua Zeng, Morgan R. Barron, Eric C. Cheon, Akilesh Honasoge, Yanfei Xu, Sharbani Phukan, Maureen Sadim, David J. Bentrem, Boris Pasche, Paul J. Grippo

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


To dissect the role of constitutively altered Tgfbr1 signaling in pancreatic cancer development, we crossed Elastase-KrasG12D (EL-Kras) mice with Tgfbr1 haploinsufficient mice to generate EL-Kras/Tgfbr1 +/- mice. Mice were euthanized at 6 to 9 months to compare the incidence, frequency, and size of precancerous lesions in the pancreas. Only 50% of all EL-Kras/Tgfbr1+/- mice developed preinvasive lesions compared with 100% of EL-Kras (wild-type Tgfbr1) mice. The frequency of precancerous lesions was 4-fold lower in haploinsufficient than in control mice. Paradoxically, the precancerous lesions of EL-Kras/Tgfbr1+/- mice were considerably larger than those in EL-Kras mice. Yet, the mitotic index of precancerous cells and the observable levels of fibrosis, lipoatrophy, and lymphocytic infiltration were reduced in EL-Kras/Tgfbr1+/- mice. We conclude that Tgfbr1 signaling promotes the development of precancerous lesions in mice. These findings suggest that individuals with constitutively decreased TGFBR1 expression may have a decreased risk of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)9169-9174
Number of pages6
JournalCancer Research
Issue number24
StatePublished - Dec 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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