| First Author | Adrian K | Year | 2009 |
| Journal | Cancer Res | Volume | 69 |
| Issue | 24 | Pages | 9169-74 |
| PubMed ID | 19951995 | Mgi Jnum | J:155392 |
| Mgi Id | MGI:4413608 | Doi | 10.1158/0008-5472.CAN-09-1705 |
| Citation | Adrian K, et al. (2009) Tgfbr1 haploinsufficiency inhibits the development of murine mutant Kras-induced pancreatic precancer. Cancer Res 69(24):9169-74 |
| abstractText | To dissect the role of constitutively altered Tgfbr1 signaling in pancreatic cancer development, we crossed Elastase-Kras(G12D) (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. |
