Estradiol-induced IP(3) mediates the estrogen receptor activity expressed in human cells.
The recent findings that estradiol-induced IP(3)/PKC-alpha signalling pathway triggers DNA synthesis in HepG2 cells, containing estrogen receptor unable to stimulate gene transactivation, raises the hypothesis that this pathway represents an alternative signalling present when the amount of estrogen receptor (ER) is insufficient to mediate genomic effects. beta-estradiol-stimulated DNA synthesis and target gene expression have been studied in HepG2 and, ER-alpha or ER-beta negative, HeLa cells. We also examined whether either receptor is required for rapid effects of estrogen on DNA synthesis. Finally, the consequences of increased ER expression on estrogen-induced DNA synthesis and synthetic target gene expression have been evaluated. Our data indicate that the E2-induced IP(3) production is dependent on expression of either ER-alpha or ER-beta in both HepG2 and HeLa cells. Moreover, inhibition of the IP(3) second messenger pathway blocks E2-induced cellular actions suggesting that this second messenger is responsible for estrogen's rapid, non-genomic effects on both DNA synthesis and gene expression.
Marino
M
M
Dipartimento di Biologia, Università Roma Tre v.le Marconi 446, 00146 Roma, Italy. m.marino@uniroma3.it
Distefano
E
E
Trentalance
A
A
Smith
C L
CL
D015153:Blotting, Western; D004261:DNA Replication / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology* / Q000502:physiology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006367:HeLa Cells; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism / Q000494:pharmacology* / Q000502:physiology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology; D051571:Protein Kinase C-alpha; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007295:Inositol Phosphates; D007527:Isoenzymes; D011960:Receptors, Estrogen; C052128:inositol 3-phosphate; D004958:Estradiol; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha