Abstract 2385: Activated Kras and INK4a/Arf deficiency cooperate to produce pancreatic cancer involved with Notch and NF-κB pathways

Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. Therefore, novel strategies for the prevention and treatment are urgently needed. Kras mutations are observed in 80%-90% of pancreatic cancer. Oncogenic Kras is involved with the initiation or early phase of PDAC. To understand the molecular mechanisms, several mouse models of PDAC have been generated by targeting a conditionally mutated KrasG12D to recapitulate the progression of PDAC. It was previously shown that one mouse model which activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic PDAC. However, the molecular mechanism(s) by which Kras and Ink4a/Arf deficiency contribute to PDAC has not been fully elucidated. Here, we assessed the molecular alterations in mice which are activated Kras and Ink4a/Arf deficiency. For the first time, we demonstrated that deletion of Ink4a/Arf in Kras expressing mice leads to PDAC partly through Notch and NF-κB signaling pathways. Moreover, we show that several miRNAs, such as miR-200 family and miR-34 could partially play roles in tumorigenesis in activated Kras and Ink4a/Arf deficiency mice. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2385. doi:10.1158/1538-7445.AM2011-2385