Document Detail


Characterization of a human melanoma cell line with non-oestrogen receptor dependent tamoxifen resistance.
MedLine Citation:
PMID:  10661763     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
E F McClay; J A Jones
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Melanoma research     Volume:  9     ISSN:  0960-8931     ISO Abbreviation:  Melanoma Res.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-02-29     Completed Date:  2000-02-29     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  9109623     Medline TA:  Melanoma Res     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  531-7     Citation Subset:  IM    
Affiliation:
Department of Medicine, Hollings Cancer Center, Medical University of South Carolina, Charleston 29425, USA. emcclay@ucsd.edu
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents, Hormonal / 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:
CA-51251/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
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

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