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Modulation of Platelet-derived Growth Factor Receptor Function in BP3T3, a Chemically Transformed BALB/c-3T3 Cell Line¹

Division of Oncology, Children's Hospital of Philadelphia, and the Department of Pediatrics, University of Pennsylvania, Philadelphia, Pennsylvania 19104

BP3T3, a clonal benzo(a)pyrene-transformed BALB/c-3T3 cell, has been shown to be conditionally responsive to platelet-derived growth factor (PDGF)-stimulated DNA synthesis. PDGF stimulates DNA synthesis in BP3T3 cell cultures maintained in 0.5% platelet-poor plasma, but pretreatment with 10% serum or 10 µg/ml insulin inhibits PDGF-modulated DNA synthesis. BALB/c-3T3 cells remain mitogenically responsive irrespective of pretreatment with serum or insulin. The present study demonstrates that pretreatment with serum or insulin inhibits BP3T3 cell DNA synthesis by affecting receptor function. Insulin and serum, however, act through different mechanisms. Pretreatment with serum for 3 or more days down-modulated the BP3T3 cell PDGF receptor, resulting in both inhibition of PDGF binding and inhibition of PDGF-stimulated receptor autophosphorylation. In contrast, treatment of nontransformed BALB/c-3T3 cells with serum for 3 or more days did not down-modulate the PDGF receptor. Pretreatment of BP3T3 cells with insulin did not inhibit PDGF binding to BP3T3 cells but did inhibit PDGF-stimulatable tyrosine-specific receptor autophosphorylation. This effect was minimal to nonexistent in BALB/c-3T3 cell cultures. It appears likely that pretreatment of BP3T3 cells with insulin either inhibits the tyrosine kinase activity of the PDGF receptor or activates receptor dephosphorylation.

¹ This work was supported by National Institute of Health Grants CA 34162 (C. D. S.) and CA 44441 (S. B.) and Grant 2275 (C. D. S.) from the Council for Tobacco Research U.S.A. P. G. was supported by an Alberta Heritage Foundation for Medical Research Award, C. D. S. by "The Eagle's Fly for Leukemia" campaign, and S. B. by the Joseph Stokes, Jr., Research Institute.

² Present address: Department of Pediatrics, University of Alberta, Edmonton, Alberta T6G2R7, Canada.

³ To whom requests for reprints should be addressed, at Children's Hospital of Philadelphia, 34th and Civic Center Boulevard, Philadelphia, PA 19104.

Received 12/19/88. Revised 3/21/89. Accepted 3/28/89.