Insulin-like growth factor I overexpression in human pancreatic cancer: evidence for autocrine and paracrine roles.
We assessed the potential roles of insulin-like growth factor-I (IGF-I) and the IGF-I receptor (IGF-IR) in human pancreatic cancer. IGF-I enhanced the growth of ASPC-1 and COLO-357 human pancreatic cancer cells, and this effect was significantly inhibited by a highly specific monoclonal anti-IGF-IR antibody (alpha IR3). Both cell lines expressed mRNA transcripts for IGF-IR, and basal cell growth was significantly reduced by an IGF-IR antisense oligodeoxynucleotide. IGF-I mRNA transcripts were not detected in either cell line or in two additional pancreatic cancer cell lines. In contrast, analysis of 12 pancreatic cancers revealed a 32-fold increase (P < 0.01) in IGF-I mRNA levels by comparison with the low levels observed in the normal pancreas. By in situ hybridization, IGF-I mRNA grains were present in both the cancer cells and in the surrounding connective tissue. Six of the cancers exhibited a 4.4-fold increase in IGF-IR mRNA levels. These findings suggest that IGF-I may participate in aberrant autocrine and paracrine activation of IGF-IR in pancreatic cancer in vivo.
Bergmann
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U
Department of Medicine, University of California, Irvine 92717, USA.
Funatomi
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Yokoyama
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Beger
H G
HG
Korc
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M
D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000502:physiology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D012334:RNA, Neoplasm; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1