Potentiation of genomic actions of estrogen by membrane actions in mcf-7 cells and the involvement of protein kinase C activation.
It is now well established that estrogens (E) have at least two kinds of actions: genomic and nongenomic. But the relationship between these actions has hardly been explored. In this study we investigated this relationship in MCF-7 cells, a human breast cancer cell line, and explored the possible involvement of protein kinase C (PKC) signaling pathways. For this purpose a two-pulse paradigm was used: cells were treated with 17beta-estradiol (E), E conjugated with bovine serum albumin (E-BSA or fE'), or other test agents in the first pulse and with E in the second pulse following a 4-h interval. An E-BSA+E paradigm was used to show that replacement of E with the membrane-impermeable E-BSA in the first pulse could potentiate genomic actions of E, in the second pulse. To investigate involvement of signaling pathways, two PKC activators, phorbol 12,13-diacetate (PDAc) or phorbol 12-myristate 13-acetate (PMA), and inhibitors (chelerythrine chloride and H7-dihydrochloride) were used to replace E or E-BSA in the first pulse. PDAc was as effective as E or E-BSA in potentiating the genomic action of E in the second pulse, while PMA was almost without an effect. Conversely, the potentiating effects of E-BSA and PDAc were blocked by chelerythrine chloride but, interestingly, not by H7. The exact reason underlying these differences is not known. In summary, in MCF-7 cells a membrane action of E can potentiate a later genomic action and involves PKC signaling.
Devidze
Nino
N
Laboratory of Neurobiology and Behavior, The Rockefeller University, New York, NY 10021, USA. devidzn@rockfeller.edu
Pfaff
Donald W
DW
Kow
Lee-Ming
LM
D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002463:Cell Membrane Permeability; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects* / Q000502:physiology
D004791:Enzyme Inhibitors; D012710:Serum Albumin, Bovine; D004958:Estradiol; D011493:Protein Kinase C