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

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

The EGF Family of ligands and receptors plays an important role in the pathogenesis of pancreatic clinical 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). HKR-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.

Original languageEnglish (US)
Pages (from-to)514-523
Number of pages10
JournalInternational Journal of Cancer
Volume120
Issue number3
DOIs
StatePublished - Feb 1 2007

Keywords

  • Epidermal growth factor
  • Heregulin
  • Pancreatic cancer
  • Phosphorylation
  • Tyrosine kinase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kolb, A., Kleeff, J., Arnold, N., Giese, N. A., Giese, T., Korc, M., & Friess, H. (2007). Expression and differential signaling of heregulins in pancreatic cancer cells. International Journal of Cancer, 120(3), 514-523. https://doi.org/10.1002/ijc.22360