| First Author | Moorehead RA | Year | 2003 |
| Journal | Oncogene | Volume | 22 |
| Issue | 6 | Pages | 853-7 |
| PubMed ID | 12584565 | Mgi Jnum | J:82326 |
| Mgi Id | MGI:2652293 | Doi | 10.1038/sj.onc.1206188 |
| Citation | Moorehead RA, et al. (2003) Transgenic overexpression of IGF-II induces spontaneous lung tumors: a model for human lung adenocarcinoma. Oncogene 22(6):853-7 |
| abstractText | Elevated levels of insulin-like growth factor (IGF)-II are associated with a poor prognosis in human pulmonary adenocarcinoma; however, a causal role for IGF-II in pulmonary adenocarcinoma has not been demonstrated. Here, we show that transgenic overexpression of IGF-II in lung epithelium induces lung tumors in 69% of mice older than 18 months of age. These tumors displayed morphological characteristics of human pulmonary adenocarcinoma such as their epithelial origin, tubulo-acinar architecture and expression of TTF-1, SP-B and proSP-C. Examination of signaling molecules downstream of the IGF-IR showed the activation of either the Erk1/Erk2 or p38 MAPK pathways, but not both, within the lung tumors. Notably, all lung tumors contained high levels of phosphorylated CREB, suggesting that both the Erk1/Erk2 and p38 MAPK pathways converged on this transcription factor. Moreover, IGF-II induced proliferation and CREB phosphorylation in human lung cancer cell lines, suggesting that IGF-II and CREB also contribute to the growth of human lung tumors. Thus, IGF-II is an important genetic factor in the development of lung tumorigenesis, in which activation of CREB is a ubiquitous event. The MMTV-IGF-II transgenic mice provide a critical model for elucidating the role of IGF-II in this fatal human disease. |
