Overexpression of acidic and basic fibroblast growth factors in human pancreatic cancer correlates with advanced tumor stage.
Acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) are mitogenic polypeptides that may contribute to cancer cell proliferation. In the present study we examined aFGF and bFGF expression in human pancreatic cancer. Northern blot analysis of total RNA isolated from 12 pancreatic cancers revealed elevated aFGF and bFGF mRNA levels in 12 and 10 samples, respectively, by comparison with the normal human pancreas. Immunostaining demonstrated the presence of aFGF and bFGF in many cancer cells and in the atrophic acini and ducts adjacent to the cancer cells, but to a much lesser extent in the surrounding fibroblasts. By in situ hybridization, both mRNA moieties colocalized with their respective proteins and were abundant in many cancer cells. Immunoblotting confirmed that cancer tissues with increased aFGF and bFGF immunoreactivity contained elevated levels of both proteins. To determine the significance of aFGF and bFGF expression in the pancreatic cancer cells, immunohistochemical analysis of 78 human pancreatic carcinomas was performed. aFGF and bFGF immunoreactivity was present in the cancer cells in 47 (60%) and 44 (56%) of the tumors, respectively. There was a significant correlation between the presence of either aFGF or bFGF in the cancer cells and advanced tumor stage, and the presence of bFGF and shorter patient survival. These data suggest that aFGF and bFGF are overexpressed in a significant proportion of human pancreatic carcinoma cells and that this overexpression may contribute to disease progression.
Yamanaka
Y
Y
Department of Medicine, University of California, Irvine 92717.
Friess
H
H
Buchler
M
M
Beger
H G
HG
Uchida
E
E
Onda
M
M
Kobrin
M S
MS
Korc
M
M
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D015152:Blotting, Northern; D015342:DNA Probes; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000032:analysis / Q000096:biosynthesis*; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010179:Pancreas / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D015347:RNA Probes; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism*; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D015342:DNA Probes; D015347:RNA Probes; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1