Estrogen-induced mitogenesis of MCF-7 cells does not require the induction of mitogen-activated protein kinase activity.
Estrogen mediates the transcription of responsive genes via its interaction with the estrogen receptor (ER). This ligand-dependent transcriptional activity has been the mechanistic basis for understanding estrogen-induced proliferation. However, recent reports suggest that estrogen stimulation results in activation of the mitogen-activated protein kinase (MAPK) cascade in an ER-dependent manner suggesting that mitogenesis may be mediated through this cytoplasmic signaling cascade. In this study, we demonstrate that estrogen stimulation of MCF-7 cells does not activate MAPK regardless of hormone concentration, serum concentration, or cell density. We also excluded the activation of MAPK through autocrine effects after estrogen treatment. Finally, concentrations required for estrogen-induced mitogenesis and estrogen-mediated transcription were shown to be the same. These results support transcriptional activation as the primary mechanism for estrogen-mediated mitogenesis.
Lobenhofer
E K
EK
Program in Cell and Molecular Biology, Duke University Medical Center, Durham, NC 27710, USA.
Marks
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JR
D019898:Autocrine Communication / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008934:Mitogens / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D004965:Estrogen Antagonists; D004967:Estrogens; D006133:Growth Substances; D007106:Immune Sera; D008934:Mitogens; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases