| First Author | Till JE | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 19 | Pages | 5349-5359 |
| PubMed ID | 28760854 | Mgi Jnum | J:245682 |
| Mgi Id | MGI:5915893 | Doi | 10.1158/0008-5472.CAN-17-0061 |
| Citation | Till JE, et al. (2017) Oncogenic KRAS and p53 Loss Drive Gastric Tumorigenesis in Mice That Can Be Attenuated by E-Cadherin Expression. Cancer Res 77(19):5349-5359 |
| abstractText | Gastric adenocarcinoma is the third leading cause of cancer-related death worldwide, but no models exist to readily investigate distant metastases that are mainly responsible for mortality in this disease. Here we report the development of a genetically engineered mouse model of gastric adenocarcinoma tumorigenesis based on KrasG12D expression plus inactivation of E-cadherin (Cdh1) and p53 in the gastric parietal cell lineage. Intestinal and diffuse gastric tumors arise rapidly in this model that displays a median survival of 76 days. Tumors occur throughout the stomach, with metastases documented in lymph nodes, lung, and liver. Mice otherwise identical but retaining one wild-type Cdh1 allele exhibited longer survival with only 20% penetrance of invasive tumors and no apparent lung or liver metastases. Notably, increased RAS activity and downstream MAPK signaling was observed in stomachs only when E-cadherin was absent. This model offers a valuable tool to investigate gastric adenocarcinoma subtypes where RAS/MAPK pathway activation and E-cadherin attenuation are common. Cancer Res; 77(19); 5349-59. (c)2017 AACR. |
