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

Oncogene. 1997 Sep 18;15(12):1417-24. doi: 10.1038/sj.onc.1201307.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Cell Division / drug effects
  • Child
  • Child, Preschool
  • Female
  • Fibroblast Growth Factor 5
  • Fibroblast Growth Factors / biosynthesis*
  • Fibroblast Growth Factors / pharmacology*
  • Humans
  • Kinetics
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Pancreas / metabolism*
  • Pancreatic Neoplasms / metabolism*
  • RNA, Messenger / biosynthesis
  • Receptors, Fibroblast Growth Factor / biosynthesis
  • Receptors, Fibroblast Growth Factor / physiology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Stromal Cells / metabolism
  • Transcription, Genetic*
  • Tumor Cells, Cultured


  • FGF5 protein, human
  • RNA, Messenger
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factor 5
  • Fibroblast Growth Factors
  • Calcium-Calmodulin-Dependent Protein Kinases