The intracellular specific 17beta-estradiol binding in the human breast cancer cell line, MCF-7, was shown to be modified by prolactin. Both ovine and human prolactin doubled the estradiol receptor (E2R) level, but the latter was at least 10 times more stimulatory on a concentration basis. Most of the E2R complex (approximately 80%) was transported to the nucleus, and the prolactin stimulation was reflected in an elevated nuclear uptake of the tritiated 17beta-estradiol. Neither ovine nor human prolactin altered the growth rate of the cells when E2R stimulation was maximal. Insulin (10 mug/ml) stimulated tritiated thymidine incorporation and total DNA content but had no apparent effect on E2R concentration. At 10(-4) M, N6,O2'-dibutyrylcyclicadenosine 3':5'-monophosphate increased insulin stimulation of tritiated thymidine incorporation and brought about a prolactin stimulation of apparent DNA synthesis. Theophylline (10(-3) M) blocked both of these effects of N6,O2'-dibutyrylcyclicadenosine 3':5'-monophosphate. The possible mechanism implicating prolactin as an effector of differentiation and growth of MCF-7 cells is discussed.
3',5'-Cyclic-AMP Phosphodiesterases Breast Neoplasms