Document Detail


The development and characterization of Vinca alkaloid-resistant Caco-2 human colorectal cell lines expressing mdr-1.
MedLine Citation:
PMID:  8094716     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several novel cell lines with variable resistance to Vinca alkaloids have been derived from the Caco-2 human colorectal carcinoma cell line. Parental Caco-2 cells were found by PCR analysis and immunofluorescence studies to produce a low amount of the mdr-1 gene product (P-glycoprotein) that may well be clinically significant. These cells, which were initially highly sensitive to desacetylvinblastine sulfate (DAVLB sulfate) were selected, without mutagenesis, through continuous culture with increasing concentrations of DAVLB sulfate over a 335-day period. This selection resulted in cell lines that displayed an mdr (multiple-drug-resistance) cross-resistance profile that could be reversed with agents such as verapamil and vindoline. During the selection process the amount of mdr-1 mRNA present, the extent of gene amplification and the amount of gp170 expressed all correlated well with the level of drug resistance. However, this correlation does not hold in the absence of selective pressure for the more resistant cell lines where gene amplification and the amount of P-glycoprotein present remained constant while the level of drug resistance and the amount of mdr-1 mRNA present declined. These cell lines are potential models for studying mdr-I gene expression and drug resistance in human epithelial malignancies.
Authors:
J Hoskins; S V DeHerdt; R E Moore; T F Bumol
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Publication Detail:
Type:  In Vitro; Journal Article    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  53     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  1993 Feb 
Date Detail:
Created Date:  1993-03-23     Completed Date:  1993-03-23     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  680-8     Citation Subset:  IM    
Affiliation:
Department of Cancer Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Cell Division / drug effects
Colorectal Neoplasms / genetics,  pathology*
Drug Resistance*
Gene Amplification
Gene Expression
Humans
Membrane Glycoproteins / genetics*
Molecular Sequence Data
Oligodeoxyribonucleotides / chemistry
P-Glycoprotein
Polymerase Chain Reaction
RNA, Messenger / genetics
RNA, Neoplasm / genetics
Tumor Cells, Cultured
Vinca Alkaloids / pharmacology*
Chemical
Reg. No./Substance:
0/Membrane Glycoproteins; 0/Oligodeoxyribonucleotides; 0/P-Glycoprotein; 0/RNA, Messenger; 0/RNA, Neoplasm; 0/Vinca Alkaloids

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


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