Anunexpected observation was the ability of mitogens, such as concanavalin A and Epstein-Barr virus, to increase expression of insulin receptors (IRs) in lymphocytes. Moreover, human lymphocyte-derived malignant cells, such as the IM-9 cells (B-type lymphoblasts derived from a subject with multiple myeloma), are abundantly endowed with high-affinity IRs. IR up-regulation in these cells has no major effect on cell metabolism, but coincides with the development of increased sensitivity to the nonmetabolic effects of insulin. A role for IR in tumor progression was suggested by studies indicating that IR is overexpressed in several tumors, including breast, colon, lung, ovary, and thyroid carcinomas.
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