| Aryl hydrocarbon receptor-mediated antiestrogenicity in MCF-7 cells: modulation of hormone-induced cell cycle enzymes. | |
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MedLine Citation:
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PMID: 9705214 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) inhibits 17beta-estradiol (E2) mammary tumor growth in rodents and in MCF-7 human breast cancer cells; however, the cell cycle genes/proteins which are inhibited have not been determined. Initial studies showed that treatment of MCF-7 cells with 10 nM E2 significantly increased cyclin D1 (protein and mRNA), cdk2- and cdk4-dependent kinase activities, and hyperphosphorylation of retinoblastoma (RB) protein. In contrast to results of recent studies (M. D. Planas-Silva and R. A. Weinberg, 1997, Mol. Cell. Biol. 17, 4059-4069), E2 induced dissociation of both cdk2 and cdk4 proteins from the p21 protein complex and significantly increased cdk7-dependent kinase activity. Treatment of MCF-7 cells with E2 also induced cdc25A phosphatase protein, which was accompanied by increased cdk2 and cdk4 proteins containing unphosphorylated tyrosine residues. Although TCDD alone has minimal effects on cell cycle proteins/enzymes, several E2-induced responses were significantly inhibited in MCF-7 cells cotreated with E2 plus TCDD. For example, TCDD significantly inhibited E2-induced hyperphosphorylation of RB, cyclin D1 protein, and cdk2-, cdk4-, and cdk7-dependent kinase activities. Inhibition of E2-induced cdk4-dependent kinase activity by TCDD may be related to the parallel decrease of E2-induced cyclin D1 protein, and inhibition of induced cdk2- and cdk4-dependent kinase activities may be due to significantly increased p21 levels in cells cotreated with TCDD plus E2. These results demonstrate that the antiestrogenic activity of TCDD is due to downregulation of several E2-induced cell cycle proteins/activities and this illustrates the complex cross talk between the aryl hydrocarbon and the E2 receptor signaling pathways. |
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Authors:
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W Wang; R Smith; S Safe |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Archives of biochemistry and biophysics Volume: 356 ISSN: 0003-9861 ISO Abbreviation: Arch. Biochem. Biophys. Publication Date: 1998 Aug |
Date Detail:
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Created Date: 1998-09-16 Completed Date: 1998-09-16 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 0372430 Medline TA: Arch Biochem Biophys Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 239-48 Citation Subset: IM |
Copyright Information:
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Copyright 1998 Academic Press. |
Affiliation:
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Department of Veterinary Pathobiology, Texas A&M University, College Station, Texas, 77843-4466, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Breast Neoplasms
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enzymology*,
metabolism* CDC2-CDC28 Kinases* Cell Cycle Proteins / drug effects* Cyclin D1 / metabolism Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases / metabolism Cyclins / metabolism Estradiol / pharmacology* Estrogen Antagonists / pharmacology* Female Humans Microtubule-Associated Proteins / metabolism Phosphorylation Protein Tyrosine Phosphatases / metabolism Protein-Serine-Threonine Kinases / metabolism Proto-Oncogene Proteins* Receptors, Aryl Hydrocarbon / physiology* Retinoblastoma Protein / metabolism Tetrachlorodibenzodioxin / pharmacology Tumor Cells, Cultured Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins* Tyrosine / metabolism cdc25 Phosphatases* |
| Grant Support | |
ID/Acronym/Agency:
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CA-64081/CA/NCI NIH HHS; ES04176/ES/NIEHS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CDKN1A protein, human; 0/Cell Cycle Proteins; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Estrogen Antagonists; 0/Microtubule-Associated Proteins; 0/Proto-Oncogene Proteins; 0/Receptors, Aryl Hydrocarbon; 0/Retinoblastoma Protein; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; 1746-01-6/Tetrachlorodibenzodioxin; 50-28-2/Estradiol; 55520-40-6/Tyrosine; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases; EC 2.7.11.22/cyclin-dependent kinase-activating kinase; EC 3.1.3.48/CDC25A protein, human; EC 3.1.3.48/Protein Tyrosine Phosphatases; EC 3.1.3.48/cdc25 Phosphatases |
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