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Alteration in Insulin Receptor Expression Accompanying Differentiation of HL-60 Leukemia Cells

Department of Medicine, Divisions of Hematology/Oncology and Endocrinology/Metabolism, East Carolina University School of Medicine, Greenville, North Carolina 27834

Differentiation of leukemic cells in vitro is characterized by the sequential appearance of morphological, functional, and biochemical markers of maturation. The interaction of insulin with its receptor may be a regulator of growth and differentiation of leukemic cells. Human promyelocytic leukemia cells (HL-60) demonstrate specific reversible insulin binding consistent with properties of human insulin receptor. HL-60 cells treated with 500 µM N₆,O₂-dibutyryl adenosine 3',5'-cyclic monophosphate, 1 µM 1,25-dihydroxyvitamin D₃, or 41 nM phorbol-12-myristate-13-acetate expressed monocytic markers of differentiation and an increase in insulin receptor expression. The change in insulin receptor expression with 1 µM 1,25-dihydroxyvitamin D₃ and N₆,O₂-dibutyryl adenosine 3',5'-cyclic monophosphate induction was further characterized by Scatchard analysis. High affinity binding (K_d) constant was not altered, and the change in binding was attributed to receptor number. Commitment to increased insulin receptor expression was demonstrated after 1-h exposure to 1 µM 1,25-dihydroxyvitamin D₃. Agents which induced granulocytic differentiation, such as 160 mM dimethyl sulfoxide and 100 nM retinoic acid, significantly decreased insulin receptor expression compared to monocytic inducing agents. This difference in insulin receptor expression correlated with binding characteristics in normal human peripheral granulocyte and monocytes. The HL-60 cell line offers a model for the study of the molecular events which lead to the contrasting insulin receptor expression during myeloid and monocytoid hematopoiesis.

¹ To whom requests for reprints should be addressed, at Department of Medicine, Division of Hematology/Oncology, East Carolina University School of Medicine, Greenville, NC 27834.

² Recipient of support in part by a grant from the NIH (R.O. No. 2ROL AM 32585-03 Met).

Received 6/17/85. Revised 8/21/85. Revised 11/13/85. Accepted 11/15/85.