| First Author | Cadoret A | Year | 2005 |
| Journal | Int J Cancer | Volume | 114 |
| Issue | 4 | Pages | 668-72 |
| PubMed ID | 15609331 | Mgi Jnum | J:96173 |
| Mgi Id | MGI:3529639 | Doi | 10.1002/ijc.20805 |
| Citation | Cadoret A, et al. (2005) c-myc-induced hepatocarcinogenesis in the absence of IGF-I receptor. Int J Cancer 114(4):668-72 |
| abstractText | Numerous tumours, including hepatocarcinomas, produce IGFs, and some depend on these growth factors in a paracrine or autocrine fashion. We have shown that c-myc-induced experimental hepatocarcinogenesis is associated with enhanced production of IGF-II. To assess the role of the IGF-I receptor (IGF-IR) in hepatocarcinogenesis, we generated conditional mutant mice that overexpressed c-myc and were knocked out for IGF-IR specifically in the liver. We compared these mice with littermate controls that also overexpressed c-myc but had wild-type IGF-IR alleles. We found that the pretumoral phase, induced by early c-myc expression and characterised by increased cell proliferation, was largely unaffected by the lack of IGF-IR. To our further surprise, hepatocellular carcinomas (HCCs) lacking IGF-IR readily developed and progressed at the same rate as control HCCs. At 9 months, all c-myc transgenic mice displayed well-differentiated multifocal tumours, regardless of whether their livers-and their tumours-were able to produce IGF-IR. Levels of IRS-1 and IRS-2 were elevated in all tumours in the presence or absence of IGF-IR, suggesting that the signalling pathway downstream of IGF-IR is activated via IGF-IR-independent mechanisms in HCC. In conclusion, the deregulation of IGF signalling pathways, which often occurs during liver tumorigenesis, does not necessarily require IGF-IRs, and hepatic IGF-IR alone may not play a determinant role in c-myc-induced hepatocarcinogenesis. (c) 2004 Wiley-Liss, Inc. |
