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EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma.

ABSTRACT: 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.

SUBMITTER: Navas C

PROVIDER: S-EPMC3601542 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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EGF receptor signaling is essential for k-ras oncogene-driven pancreatic ductal adenocarcinoma.

Navas Carolina C Hernández-Porras Isabel I Schuhmacher Alberto J AJ Sibilia Maria M Guerra Carmen C Barbacid Mariano M

Cancer cell 20120901 3

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 i ...[more]

PMID: 22975375

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