Fibroblast growth factor-5 stimulates mitogenic signaling and is overexpressed in human pancreatic cancer: evidence for autocrine and paracrine actions.
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.
Kornmann
M
M
Department of Medicine, Biological Chemistry and Pharmacology, University of California, Irvine 92697, USA.
Ishiwata
T
T
Beger
H G
HG
Korc
M
M
D000230:Adenocarcinoma / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000368:Aged; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors / Q000096:biosynthesis* / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D017154:Stromal Cells / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C496449:FGF5 protein, human; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; D051521:Fibroblast Growth Factor 5; D005346:Fibroblast Growth Factors; D017871:Calcium-Calmodulin-Dependent Protein Kinases