| First Author | Hill R | Year | 2010 |
| Journal | Cancer Res | Volume | 70 |
| Issue | 18 | Pages | 7114-24 |
| PubMed ID | 20807812 | Mgi Jnum | J:164210 |
| Mgi Id | MGI:4830907 | Doi | 10.1158/0008-5472.CAN-10-1649 |
| Citation | Hill R, et al. (2010) PTEN loss accelerates KrasG12D-induced pancreatic cancer development. Cancer Res 70(18):7114-24 |
| abstractText | KRAS mutations are found in approximately 90% of human pancreatic ductal adenocarcinomas (PDAC). However, mice genetically engineered to express Kras(G12D) from its endogenous locus develop PDACs only after a prolonged latency, indicating that other genetic events or pathway alterations are necessary for PDAC progression. The PTEN-controlled phosphatidylinositol 3-kinase (PI3K)/AKT signaling axis is dysregulated in later stages of PDAC. To better elucidate the role of PTEN/PI3K/AKT signaling in Kras(G12D)-induced PDAC development, we crossed Pten conditional knockout mice (Pten(lox/lox)) to mice with conditional activation of Kras(G12D). The resulting compound heterozygous mutant mice showed significantly accelerated development of acinar-to-ductal metaplasia (ADM), malignant pancreatic intraepithelial neoplasia (mPanIN), and PDAC within a year. Moreover, all mice with Kras(G12D) activation and Pten homozygous deletion succumbed to cancer by 3 weeks of age. Our data support a dosage-dependent role for PTEN, and the resulting dysregulation of the PI3K/AKT signaling axis, in both PDAC initiation and progression, and shed additional light on the signaling mechanisms that lead to the development of ADM and subsequent mPanIN and pancreatic cancer. |
