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Effects of 12-O-Tetradecanoylphorbol-13-acetate on Epidermal Growth Factor Receptors in BALB/c-3T3 Cells: Relationship between Receptor Modulation and Mitogenesis¹

Experimental Pathology Group, University of California, Los Alamos National Laboratory, Los Alamos, New Mexico 87545

The addition of medium containing 0.1% serum and 12-O-tetradecanoylphorbol-13-acetate (TPA) to quiescent cultures of BALB/c-3T3 cells caused a rapid decrease in the subsequent binding and accumulation of epidermal growth factor (EGF) during a 30-min exposure at 37°C. With further incubation in medium containing TPA, the rate of EGF accumulation steadily increased over time, until by 24 h it had recovered to control values. The addition of TPA with low serum did not stimulate cell cycle traverse. In contrast, when TPA was added directly to spent medium or with fresh medium containing insulin, there was a marked increase in DNA synthesis. Under these conditions the initial TPA-induced decrease in EGF accumulation persisted over a 24-h period. A Scatchard analysis indicated that TPA caused an initial decrease in receptor affinity that persisted if the cells were also stimulated to enter the cell cycle. Thus TPA appeared to have multiple effects on the modulation of the EGF receptor. The pattern of binding following addition of TPA depended on both direct actions of the promoter and an indirect action which depended on whether the promoter was added under conditions in which cell cycle traverse was stimulated.

¹ This work was supported in part by the United States Department of Energy under Contract W-7405-ENG36 with the University of California and by the United States Army Medical Research and Development Command, Fort Detrick, MD. The National Flow Cytometry and Sorting Resource was supported by NIH/DDR Grant RR0315.

² To whom requests for reprints should be addressed, at LS-4, Mail Stop M888, Los Alamos National Laboratory, Los Alamos, NM 87545.

Received 9/17/85. Revised 5/ 5/86. Accepted 6/ 3/86.