Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer: Evidence for autocrine and paracrine actions

Marko Kornmann, Toshiyuki Ishiwata, Hans G. Beger, Murray Korc

Research output: Contribution to journalArticle

89 Scopus citations

Abstract

Fibroblast growth factor (FGF)-1 and -2 are overexpressed in human pancreatic cancer. In this study the role of FGF-5 in human pancreatic cancer was investigated, as FGF-5 has a classical signal sequence for secretion not found in FGF-1 or -2. Northern blot analysis with a 306 bp FGF-5 cDNA revealed the presence of 4.0 kb and 1.6 kb FGF-5 mRNA transcripts in both normal and cancerous pancreatic tissues. Densitometric analysis indicated that 4.0 kb and 1.6 kb FGF-5 mRNA transcripts levels were increased 2.4- and 2.7-fold in the cancers by comparison with normal tissues, respectively (P < 0.002, P < 0.0001). Immunohistochemistry and in situ hybridization demonstrated that FGF-5 localized in the cancer cells, stromal fibroblast and inflitrating macrophages. FGF-5 mRNA was also detected in COLO-357 human pancreatic cancer cells. Furthermore, secreted FGF-5 protein was present in conditioned medium of COLO-357 cells. Exogeneous FGF-5 (0.37 nM) increased the growth of COLO-357 cells by 48% (P < 0.0001) and increased mitogen-activated protein kinase activity. COLO-357 cells expressed the IIIc isoform of the type I FGF receptor, the preferred FGF receptor for FGF-5. These observations suggest that FGF-5 may participate in autocrine and paracrine pathways promoting pancreatic cancer cell growth in vivo.

Original languageEnglish (US)
Pages (from-to)1417-1424
Number of pages8
JournalOncogene
Volume15
Issue number12
DOIs
StatePublished - Jan 1 1997

Keywords

  • Fibroblast growth factor receptor splice variant
  • Fibroblast growth factor-5
  • In situ hybridization
  • Mitogenic signaling
  • Pancreatic cancer
  • Protein kinases

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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