EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma.
Clinical evidence indicates that mutation/activation of EGF receptors (EGFRs) is mutually exclusive with the�presence of K-RAS oncogenes in lung and colon tumors. We have validated these observations using genetically engineered mouse models. However, development of pancreatic ductal adenocarcinomas...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2012 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/23071 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/23071 |
| Access Level: | acceso abierto |
| Palabra clave: | Genes, ras Phosphoinositide-3 Kinase Inhibitors Signal Transduction Adenocarcinoma Animals Carcinoma, Pancreatic Ductal Cell Transformation, Neoplastic Cells, Cultured Epithelial Cells ErbB Receptors Erlotinib Hydrochloride Humans Mice Mice, Transgenic Pancreas Pancreatic Neoplasms Proto-Oncogene Proteins Proto-Oncogene Proteins p21(ras) Quinazolines STAT3 Transcription Factor Tumor Suppressor Protein p53 ras Proteins |
| Sumario: | Clinical evidence indicates that mutation/activation of EGF receptors (EGFRs) is mutually exclusive with the�presence of K-RAS oncogenes in lung and colon tumors. We have validated these observations using genetically engineered mouse models. However, development of pancreatic ductal adenocarcinomas driven by K-Ras oncogenes are totally dependent on EGFR signaling. Similar results were obtained using human pancreatic tumor cell lines. EGFRs were also essential even in the context of pancreatic injury and absence of p16Ink4a/p19Arf. Only loss of p53 made pancreatic tumors independent of EGFR signaling. Additional inhibition of PI3K and STAT3 effectively prevented proliferation of explants derived from these p53-defective pancreatic tumors. These findings may provide the bases for more rational approaches to treat pancreatic tumors in the clinic. |
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