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

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.

• Authors: U Stein, W Walther, R H Shoemaker
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 122 Issue 5 Pg. 275-82 ( 1996) ISSN: 0171-5216 [Print] Germany
• PMID: 8609150 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents, Phytogenic
• Vincristine
• Chloramphenicol O-Acetyltransferase

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Chloramphenicol O-Acetyltransferase (genetics)
• Colonic Neoplasms (drug therapy, pathology)
• Dose-Response Relationship, Drug
• Drug Resistance, Multiple (genetics)
• Humans
• Mutation
• Promoter Regions, Genetic
• Tumor Cells, Cultured
• Vincristine (pharmacology)