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 3.5-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 10(4) to 2.28 X 10(4) 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 10(4) 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.