EGF Receptor Is Required for KRAS-Induced Pancreatic Tumorigenesis

Christine M. Ardito, Barbara M. Grüner, Kenneth K. Takeuchi, Clara Lubeseder-Martellato, Nicole Teichmann, Pawel K. Mazur, Kathleen E. DelGiorno, Eileen S. Carpenter, Christopher J. Halbrook, Jason C. Hall, Debjani Pal, Thomas Briel, Alexander Herner, Marija Trajkovic-Arsic, Bence Sipos, Geou Yarh Liou, Peter Storz, Nicole R. Murray, David W. Threadgill, Maria SibiliaM. Kay Washington, Carole L. Wilson, Roland M. Schmid, Elaine W. Raines, Howard C. Crawford, Jens T. Siveke

Research output: Contribution to journalArticlepeer-review

328 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)304-317
Number of pages14
JournalCancer cell
Issue number3
StatePublished - Sep 11 2012

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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