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

87 Citations (Scopus)

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
StatePublished - 1997
Externally publishedYes

Fingerprint

Fibroblast Growth Factor 5
Pancreatic Neoplasms
Fibroblast Growth Factor 1
Fibroblast Growth Factor Receptors
Messenger RNA
Fibroblast Growth Factor 2
Stromal Cells
Conditioned Culture Medium
Growth
Protein Sorting Signals
Mitogen-Activated Protein Kinases
Northern Blotting
In Situ Hybridization

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
  • Cancer Research
  • Genetics

Cite this

Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer : Evidence for autocrine and paracrine actions. / Kornmann, Marko; Ishiwata, Toshiyuki; Beger, Hans G.; Korc, Murray.

In: Oncogene, Vol. 15, No. 12, 1997, p. 1417-1424.

Research output: Contribution to journalArticle

Kornmann, Marko ; Ishiwata, Toshiyuki ; Beger, Hans G. ; Korc, Murray. / Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer : Evidence for autocrine and paracrine actions. In: Oncogene. 1997 ; Vol. 15, No. 12. pp. 1417-1424.
@article{ffdd04368e684fa4a2acb192f6ca046d,
title = "Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer: Evidence for autocrine and paracrine actions",
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.",
keywords = "Fibroblast growth factor receptor splice variant, Fibroblast growth factor-5, In situ hybridization, Mitogenic signaling, Pancreatic cancer, Protein kinases",
author = "Marko Kornmann and Toshiyuki Ishiwata and Beger, {Hans G.} and Murray Korc",
year = "1997",
language = "English (US)",
volume = "15",
pages = "1417--1424",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "12",

}

TY - JOUR

T1 - Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer

T2 - Evidence for autocrine and paracrine actions

AU - Kornmann, Marko

AU - Ishiwata, Toshiyuki

AU - Beger, Hans G.

AU - Korc, Murray

PY - 1997

Y1 - 1997

N2 - 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.

AB - 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.

KW - Fibroblast growth factor receptor splice variant

KW - Fibroblast growth factor-5

KW - In situ hybridization

KW - Mitogenic signaling

KW - Pancreatic cancer

KW - Protein kinases

UR - http://www.scopus.com/inward/record.url?scp=0030824603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030824603&partnerID=8YFLogxK

M3 - Article

VL - 15

SP - 1417

EP - 1424

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 12

ER -