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.