Work

Isolation and sequence of the promoter region of the human multidrug-resistance (P-glycoprotein) gene.

Year: 1987

Type: article

Abstract: Intrinsic and acquired multidrug resistance is an important problem in cancer therapy. Multidrug resistance results from overexpression of the MDR 1 gene, which encodes a drug-efflux pump called P-glycoprotein. We have isolated a 1-kilobase genomic fragment containing the major transcription initiation sites for the human MDR 1 gene. Ribonuclease protection experiments using this fragment indicate that normal human adrenal, colon, and liver cells, the human hepatoma cell line HepG2, and vinblastine-selected human KB multidrug-resistant cells initiate transcription of the MDR 1 gene at the same site within this fragment. The 0.43-kilobase region upstream from the major transcription initiation site linked to the chloramphenicol acetyltransferase gene showed promoter activity in CV-1 monkey kidney cells and in human KB cells. The putative promoter region has a consensus CAAT box and two GC box-like sequences, but no TATA sequence. This identification and isolation of promoter sequences for the MDR 1 gene will permit studies on how expression of this gene is regulated in normal human tissues and cancers.

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(18)45397-5

Authors: K Ueda, I Pastan, M M Gottesman

Institution: National Cancer Institute

Language: English

Topic: Drug Transport and Resistance Mechanisms

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430