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Expression and differential signaling of heregulins in pancreatic cancer cells
Author(s) -
Kolb Armin,
Kleeff Jörg,
Arnold Nichole,
Giese Nathalia A.,
Giese Thomas,
Korc Murray,
Friess Helmut
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.22360
Subject(s) - pancreatic cancer , erbb , erbb3 , biology , cancer research , receptor , signal transduction , adenocarcinoma , cell growth , ca19 9 , cancer , cell culture , downregulation and upregulation , microbiology and biotechnology , medicine , epidermal growth factor receptor , genetics , gene
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.