Differential Responsiveness of Normal and Simian Virus 40-Transformed BALB/c 3T3 Cells to Retinoic Acid: Rapid Enhancement of Epidermal Growth Factor Receptor Binding in A Simian Virus 40-3T3 Variant

The effects of retinoic acid on the epidermal growth factor (EGF) receptor binding and cell growth of normal and simian virus 40 (SV40)-transformed BALB/c 3T3 cells were compared under identical culture conditions. Retinoic acid induced a rapid enhancement of EGF binding to SV40-transformed cells. Half-maximal enhancement occurred at about 7 h after the cells were exposed to 20 ng/ml of retinoic acid, and maximal stimulation (from 2.5- to 33-fold over the control) was obtained after 12 h of exposure. The kd of the control and retinoic acid-treated cells was calculated to be 8.0 x 10-10 m and 8.2 x-10 m, respectively. However, the number of unoccupied EGF binding sites increased from 0.98 x 104 to 2.28 x 104 per cell. Normal 3T3 cells would not respond to retinoic acid unless they were cultured in serum-containing medium. After 96 h of exposure, only a 50% enhancement of EGF binding was observed. The EGF receptor number of the untreated normal cells was calculated to be 1.82 x 104 per cell, twice the number expressed by untreated SV40-transformed cells. The increase of EGF receptor number caused by retinoic acid in SV40-transformed cells was blocked by either actinomycin D or cycloheximide treatment. These results indicated that SV40 transformation of BALB/c 3T3 cells altered the regulatory mechanism governing the complement of cell surface EGF receptors.