Vincristine induction of mutant and wild-type human multidrug-resistance promoters is cell-type-specific and dose-dependent

Journal of Cancer Research and Clinical Oncology
U SteinR H Shoemaker

Abstract

To investigate multidrug-resistance gene (MDR1) promoter efficacy and drug inducibility in cells with different multidrug-resistance phenotypes, multidrug-resistant HCT15 and drug-sensitive KM12 human colon carcinoma cell lines were transfected with constructs incorporating the chloramphenicol acetyltransferase (CAT) reporter gene, driven by wild-type and point-mutated MDR1 promoter regions. The basal CAT expression level in HCT15 cells was markedly elevated compared to KM12 cells. CAT induction by vincristine was dose-dependent over a broad concentration range (40-500 ng/ml) in both lines. The induction levels were related to the cells' MDR phenotype, with the multidrug-resistant HCT15 cells showing the greater effect. In both cell types, basal and drug-induced CAT expression were significantly enhanced by the point-mutated promoter regions. The findings support the possible exploitation of the MDR1 promoter for construction of drug-inducible and MDR-cell-targeted expression vectors for use in gene therapy.

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Citations

Feb 22, 2002·International Journal of Cancer. Journal International Du Cancer·Ulrike SteinManfred Dietel
Dec 1, 1996·Molecular Biotechnology·W Walther, U Stein
Feb 27, 2007·Cancer Metastasis Reviews·Ying Huang
Mar 24, 2000·Trends in Genetics : TIG·D M NettelbeckR Müller
Nov 10, 2000·Advanced Drug Delivery Reviews·K J HarringtonR G Vile
Oct 14, 2005·Anti-cancer Drugs·James J MezhirRalph R Weichselbaum
Feb 19, 2002·Antimicrobial Agents and Chemotherapy·Katrina L MealeyDeborah T Kochevar
Apr 28, 2009·Advanced Drug Delivery Reviews·Wolfgang Walther, Ulrike Stein
Sep 25, 1997·International Journal of Cancer. Journal International Du Cancer·U SteinI Fichtner
Mar 20, 2002·Clinical Oncology : a Journal of the Royal College of Radiologists·Kevin J HarringtonRichard G Vile
Feb 22, 2002·International Journal of Cancer. Journal International Du Cancer·Wolfgang WaltherPeter M Schlag

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