Increased expression of insulin receptor substrate-1 in human pancreatic cancer.
Insulin receptor substrate-1 (IRS-1) is a multisite docking protein implicated in mitogenic signaling following activation of the insulin and insulin-like growth factor I receptors. In the present study we characterized IRS-1 expression in human pancreatic cancer. Northern blot analysis revealed high levels of IRS-1 mRNA transcripts in ASPC-1 and MIA PaCa-2 human pancreatic cancer cell lines, and lower levels in COLO-357, PANC-1, and T3M4 cells. Immunoblotting with anti-IRS-1 antibodies indicated that IRS-1 protein levels paralleled IRS-1 mRNA levels. Analysis of RNA isolated from normal and cancerous human pancreatic tissues indicated that 7 of 16 pancreatic cancer samples overexpressed IRS-1 mRNA transcripts by comparison with the normal pancreas and that insulin mRNA levels were abundant in many tumors. These data suggest that IRS-1 contributes to the signaling pathways that lead to excessive growth stimulation in human pancreatic cancer.
Bergmann
U
U
Division of Endocrinology, Diabetes and Metabolism, University of California, Irvine 92717, USA.
Funatomi
H
H
Kornmann
M
M
Beger
H G
HG
Korc
M
M
D015152:Blotting, Northern; D002460:Cell Line; D003110:Colonic Neoplasms; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000096:biosynthesis / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger