| Characterization of a human melanoma cell line with non-oestrogen receptor dependent tamoxifen resistance. | |
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MedLine Citation:
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PMID: 10661763 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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While investigating the mechanism of synergistic cytotoxicity between tamoxifen (TAM) and cisplatin (DDP) we developed a TAM-resistant variant of the human melanoma cell line T-289. We sought to characterize this cell line with respect to the effect of TAM resistance on a variety of different intracellular cell cycle control and apoptotic pathways. A TAM-resistant variant cell line (289 TAMs) was developed and the technique of Western analysis was to determine the changes in protein expression that occurred as a result of the development of TAM resistance. In this model, TAM resistance resulted in an increase in the detectable basal levels of cyclin E, GADD 153, p16, BAX, Bcl-XL, and wild-type and mutant p53, an increase in TAM induction of p16, and a decrease in the detectable basal levels of cyclin D1, p21 and p27. There were no detectable changes in the levels of pRb. In the TAM-resistant variant, p21 levels were essentially undetectable, while p27 was present and maintained its response to TAM Induction, albeit at a much lower level. This investigation demonstrates that the development of TAM resistance is associated with a change in the detectable levels of a variety of cell cycle control and apoptosis-related proteins. While the exact role that each change plays in the development of tamoxifen resistance remains to be determined, these data suggest that the development of resistance to a particular agent results in changes in multiple, seemingly unrelated pathways. These data have implications for future studies in both the laboratory and the clinic. |
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Authors:
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E F McClay; J A Jones |
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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: Melanoma research Volume: 9 ISSN: 0960-8931 ISO Abbreviation: Melanoma Res. Publication Date: 1999 Dec |
Date Detail:
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Created Date: 2000-02-29 Completed Date: 2000-02-29 Revised Date: 2012-06-25 |
Medline Journal Info:
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Nlm Unique ID: 9109623 Medline TA: Melanoma Res Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 531-7 Citation Subset: IM |
Affiliation:
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Department of Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston 29425, USA. emcclay@ucsd.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Hormonal
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pharmacology* Apoptosis Cell Cycle Proteins* Cyclin D1 / metabolism Cyclin E / metabolism Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p15 Cyclin-Dependent Kinase Inhibitor p21 Cyclin-Dependent Kinase Inhibitor p27 Cyclin-Dependent Kinases / metabolism Cyclins / metabolism Drug Resistance, Neoplasm* Humans Melanoma / metabolism*, pathology Microtubule-Associated Proteins / metabolism Neoplasm Proteins / metabolism Proto-Oncogene Proteins / metabolism Proto-Oncogene Proteins c-bcl-2 / metabolism Receptors, Estrogen / metabolism* Tamoxifen / pharmacology* Transcription Factors / metabolism Tumor Cells, Cultured* Tumor Suppressor Protein p53 / metabolism Tumor Suppressor Proteins* bcl-2-Associated X Protein bcl-X Protein |
| Grant Support | |
ID/Acronym/Agency:
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CA-51251/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Hormonal; 0/BAX protein, human; 0/BCL2L1 protein, human; 0/CDKN1A protein, human; 0/CDKN2B protein, human; 0/Cell Cycle Proteins; 0/Cyclin E; 0/Cyclin-Dependent Kinase Inhibitor p15; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Microtubule-Associated Proteins; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Estrogen; 0/Transcription Factors; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 10540-29-1/Tamoxifen; 136601-57-5/Cyclin D1; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 2.7.11.22/Cyclin-Dependent Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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