Cancer Cell Biology
Expression and differential signaling of heregulins in pancreatic cancer cells
Armin Kolb,
Jörg Kleeff,
Nichole Arnold,
Nathalia A. Giese,
Thomas Giese,
Murray Korc,
Helmut Friess,
Armin Kolb
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Armin Kolb and Jörg Kleeff contributed equally to the manuscript.
Search for more papers by this authorCorresponding Author
Jörg Kleeff
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Armin Kolb and Jörg Kleeff contributed equally to the manuscript.
Fax: +49-6221-56-6903.
Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, GermanySearch for more papers by this authorNichole Arnold
Departments of Medicine, and Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH
Search for more papers by this authorNathalia A. Giese
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorThomas Giese
Institute of Immunology, University of Heidelberg, Germany
Search for more papers by this authorMurray Korc
Departments of Medicine, and Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH
Search for more papers by this authorHelmut Friess
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorArmin Kolb,
Jörg Kleeff,
Nichole Arnold,
Nathalia A. Giese,
Thomas Giese,
Murray Korc,
Helmut Friess,
Armin Kolb
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Armin Kolb and Jörg Kleeff contributed equally to the manuscript.
Search for more papers by this authorCorresponding Author
Jörg Kleeff
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Armin Kolb and Jörg Kleeff contributed equally to the manuscript.
Fax: +49-6221-56-6903.
Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, GermanySearch for more papers by this authorNichole Arnold
Departments of Medicine, and Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH
Search for more papers by this authorNathalia A. Giese
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorThomas Giese
Institute of Immunology, University of Heidelberg, Germany
Search for more papers by this authorMurray Korc
Departments of Medicine, and Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH
Search for more papers by this authorHelmut Friess
Department of General Surgery, University of Heidelberg, Heidelberg, Germany
Search for more papers by this authorFax: +49-6221-56-6903.
Abstract
The EGF family of ligands and receptors plays an important role in the pathogenesis of pancreatic ductal adenocarcinoma (PDAC) and contributes to its aggressiveness. A number of molecular approaches have been developed to block these pathways, and studies have already proven the clinical benefit of this concept in PDAC. In the present study, we sought to determine the potential role of heregulins (HRGs), a family of EGF-like growth factors, in PDAC. Quantitative RT-PCR analysis revealed that HRGs as well as its signaling ErbB receptors were present in 4 of 4 human pancreatic cancer cell lines (PCCL). HRG-β1 stimulated the growth of 3 of 4 PCCL, whereas HRG-α1 inhibited cell growth in 3 of 4 cell lines. Responses towards HRGs could in part be predicted by ErbB2 and ErbB3 expression levels. HRGs induced phosphorylation of different ErbB receptors as well as activation of MAPK, p38MAPK, JNK and PI3K in a cell- and ligand-specific manner. In vivo, HRG was upregulated in pancreatic cancer tissues and localized predominantly in the cancer cells. High HRG-β levels but not HRG-α levels were associated with decreased patient survival. In conclusion, HRG is expressed by pancreatic cancer cells and influences pancreatic cancer cell growth and patient survival. © 2006 Wiley-Liss, Inc.
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