| First Author | Wang C | Year | 2016 |
| Journal | Liver Int | Volume | 36 |
| Issue | 8 | Pages | 1176-86 |
| PubMed ID | 26716908 | Mgi Jnum | J:316024 |
| Mgi Id | MGI:6832206 | Doi | 10.1111/liv.13055 |
| Citation | Wang C, et al. (2016) Activated mutant forms of PIK3CA cooperate with RasV12 or c-Met to induce liver tumour formation in mice via AKT2/mTORC1 cascade. Liver Int 36(8):1176-86 |
| abstractText | BACKGROUND & AIMS: Activating mutations of PIK3CA occur in various tumour types, including human hepatocellular carcinoma. The mechanisms whereby PIK3CA contributes to hepatocarcinogenesis remain poorly understood. METHODS: PIK3CA mutants H1047R or E545K were hydrodynamically transfected, either alone or in combination with NRasV12 or c-Met genes, in the mouse liver. RESULTS: Overexpression of H1047R or E545K alone was able to induce AKT/mTOR signalling in the mouse liver, leading to hepatic steatosis. However, none of the mice developed liver tumours over long term. In contrast, H1047R or E545K cooperated with NRasV12 or c-Met to rapidly induce liver tumour formation in mice. At the molecular level, all the tumour nodules displayed activation of AKT/mTOR and Ras/MAPK cascades. Ablation of AKT2 significantly inhibited hepatic steatosis induced by H1047R or E545K and carcinogenesis induced by H1047R/c-Met or E545K/c-Met. Furthermore, tumourigenesis induced by H1047R/c-Met was abolished in conditional Raptor knockout mice. CONCLUSIONS: Both H1047R and E545K are able to activate the AKT/mTOR pathway. An intact AKT2/mTOR complex 1 cascade is required for tumourigenesis induced by H1047R/c-Met or E545K/c-Met in the liver. |
