Document Detail


Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors.
MedLine Citation:
PMID:  1588380     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: We have shown previously that acquired tamoxifen resistance in an in vivo experimental model is associated with reduced tamoxifen accumulation, isomerization of trans-4-hydroxytamoxifen, and tamoxifen-stimulated tumor growth. The purpose of this study is to isolate and verify the presence of estrogenic tamoxifen metabolites in human breast tumors using high-performance liquid chromatography (HPLC) and mass-spectrometry (MS) techniques. PATIENTS AND METHODS: In the present study, we used HPLC and MS to identify the presence of estrogenic metabolites in tumor samples excised from athymic nude mice and in human breast tumors isolated from patients receiving adjuvant tamoxifen therapy. RESULTS: We identified the presence of metabolite E, a known estrogenic metabolite of tamoxifen, in tamoxifen-resistant MCF-7 human breast tumors implanted in athymic nude mice, as well as in tumors from patients with clinical resistance. Additionally, we separated another estrogenic metabolite, bisphenol, by HPLC, and this was also tentatively confirmed by MS analysis. CONCLUSION: These data suggest that cellular tamoxifen metabolism to estrogenic metabolites may in part contribute to stimulating the growth of hormone-responsive breast tumors following prolonged exposure to tamoxifen. Further evaluation of the relationship between cellular metabolism and acquired tamoxifen resistance is warranted.
Authors:
V J Wiebe; C K Osborne; W L McGuire; M W DeGregorio
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  10     ISSN:  0732-183X     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  1992 Jun 
Date Detail:
Created Date:  1992-06-25     Completed Date:  1992-06-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  990-4     Citation Subset:  IM    
Affiliation:
Cancer Therapy and Research Center, San Antonio, TX.
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MeSH Terms
Descriptor/Qualifier:
Animals
Breast Neoplasms / chemistry,  drug therapy*
Chromatography, High Pressure Liquid
Drug Resistance
Female
Humans
Mass Spectrometry
Mice
Mice, Nude
Neoplasm Transplantation
Tamoxifen / analogs & derivatives*,  analysis*
Chemical
Reg. No./Substance:
10540-29-1/Tamoxifen

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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