Effect of prolactin on growth and the estrogen receptor level of human breast cancer cells (MCF-7).
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.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004347:Drug Interactions; D004958:Estradiol / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism; D011388:Prolactin / Q000494:pharmacology*; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology
D004273:DNA, Neoplasm; D007328:Insulin; D009363:Neoplasm Proteins; D011960:Receptors, Estrogen; D004958:Estradiol; D003994:Bucladesine; D011388:Prolactin; D013806:Theophylline; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases