17beta-Estradiol rapidly stimulates c-fos expression via the MAPK pathway in T84 cells.
In this study, we show that 17beta-Estradiol (E2) induced the proliferation of T84 colonic carcinoma cells. We, further, investigated the mechanisms underlying this proliferation and show that E2 induced c-fos protooncogene expression in T84 cells in a timescale consistent with a rapid non-genomic action of the hormone. Furthermore, E2 rapidly phosphorylated both CREB and ELK1, transcription factors that bind to the c-fos promoter and stimulate transcription. Pretreatment with PD98059 and H89, mitogen-activated protein kinase (MAPK) pathway and protein kinase A (PKA) inhibitors, respectively showed that phosphorylation of CREB and ELK1 and subsequent c-fos induction was mediated by the MAPK pathway only. Finally, the estrogen receptor (ER) antagonist, ICI 182,780, blocked the activation of MAPK pathway, subsequent CREB and ELK1 phosphorylation and c-fos induction in T84 cells suggesting an ER dependent mechanism. Consistent with this finding, ICI 182,780 caused a substantial reduction in the proliferative effects of E2 on T84 cells.
Hennessy
Barbara A
BA
Department of Physiology, University College Cork, Ireland.
Harvey
Brian J
BJ
Healy
Vincent
V
D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators; D000077267:Fulvestrant; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D050807:ets-Domain Protein Elk-1
D000970:Antineoplastic Agents; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; C494112:ELK1 protein, human; D004791:Enzyme Inhibitors; D020847:Estrogen Receptor Modulators; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D000077267:Fulvestrant; D004958:Estradiol; D017868:Cyclic AMP-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases