Synergism between genomic and non genomic estrogen action mechanisms.
The 17beta-estradiol (E2) action mechanism for inducing target gene expression can be attributed to both the direct binding of its receptor (ER) to specific sequences, the estrogen response element (ERE), and to the interaction between ER and other DNA-binding transcription factors. At the present meagre information is available for the role played by the rapid hormone action mechanism(s) (i.e., activation of ERK, PI(3)K, PKC-alpha) in modulating E2-induced gene promoter activity. Here the involvement of the rapid non genomic mechanism in triggering the transcriptional activity of two E2-regulated target genes in human hepatoma HepG2 cells has been studied, taking into consideration the cyclin D1 (ERE-devoid) and the complement protein 3 (ERE-containing) promoter-luciferase report constructs. The results indicate that the activation of the ERK pathway is essential for the E2-induced activity of both promoters, whereas the other rapid E2-induced membrane-starting signal transduction pathways (i.e., PI(3)K and PKC-alpha) were differently required. These results permit the amplification of the E2 action mechanism by the addition of synergy between the non genomic and genomic molecular actions of the E2-induced gene transcription.
Acconcia
Filippo
F
Department of Biology, University Roma Tre, Viale G. Marconi, 446, I-00146 Rome, Italy.
Marino
Maria
M
D004789:Enzyme Activation; D004958:Estradiol / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000378:metabolism; D051571:Protein Kinase C-alpha; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004958:Estradiol; D008156:Luciferases; D019869:Phosphatidylinositol 3-Kinases; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D020928:Mitogen-Activated Protein Kinases