Format

Send to

Choose Destination
Cancer Cell. 2012 Sep 11;22(3):304-17. doi: 10.1016/j.ccr.2012.07.024.

EGF receptor is required for KRAS-induced pancreatic tumorigenesis.

Author information

1
Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794, USA.

Abstract

Initiation of pancreatic ductal adenocarcinoma (PDA) is definitively linked to activating mutations in the KRAS oncogene. However, PDA mouse models show that mutant Kras expression early in development gives rise to a normal pancreas, with tumors forming only after a long latency or pancreatitis induction. Here, we show that oncogenic KRAS upregulates endogenous EGFR expression and activation, the latter being dependent on the EGFR ligand sheddase, ADAM17. Genetic ablation or pharmacological inhibition of EGFR or ADAM17 effectively eliminates KRAS-driven tumorigenesis in vivo. Without EGFR activity, active RAS levels are not sufficient to induce robust MEK/ERK activity, a requirement for epithelial transformation.

PMID:
22975374
PMCID:
PMC3443395
DOI:
10.1016/j.ccr.2012.07.024
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center