Purpose: Insulin receptor substrates (IRSs) are essential for insulin-induced mitogenic effects on several cell types but theyalso are involved in cell transformation.We investigated whether the differential constitutive expression and potential distinctdownstream signaling events of IRS-1 and IRS-2 might be related to discrete tumourigenic phenotypes of three humanuterine leiomyosarcoma cell lines, one of which was specifically isolated for the present study. The gene discussed is INS; the disease is leiomyosarcoma.