INCREASED EXPRESSION OF INSULIN-RECEPTOR SUBSTRATE-1 IN HUMAN PANCREATIC-CANCER

Insulin receptor substrate-1 (IRS-1) is a multisite docking protein im plicated in mitogenic signaling following activation of the insulin an d insulin-like growth factor I receptors. In the present study we char acterized IRS-1 expression in human pancreatic cancer. Northern blot a nalysis revealed high levels of IRS-1 mRNA transcripts in ASPC-1 and M IA PaCa-2 human pancreatic cancer cell lines, and lower levels in COLO -357. PANC-1, and T3M4 cells. Immunoblotting with anti-IRS-1 antibodie s indicated that IRS-1 protein levels paralleled IRS-1 mRNA levels. An alysis of RNA isolated from normal and cancerous human pancreatic tiss ues indicated that 7 of 16 pancreatic cancer samples overexpressed IRS -1 mRNA transcripts by comparison with the normal pancreas and that in sulin mRNA levels were abundant in many tumors. These data suggest tha t IRS-1 contributes to the signaling pathways that lead to excessive g rowth stimulation in human pancreatic cancer. (C) 1996 Academic Press, Inc.