The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation

K. Ueda, D. P. Clark, C. J. Chen, I. B. Roninson, M. M. Gottesman, I. Pastan

Research output: Contribution to journalArticle

Abstract

Multidrug resistance in human KB carcinoma cells selected for resistance to colchicine, vinblastine, or adriamycin results from overexpression, and frequently amplification, of a specific gene (mdr1). Overlapping cDNA clones representing a complete 4.7-kilobase mdr1 transcript have been obtained from multidrug-resistant KB cells. Primer extension and S1 nuclease protection experiments show that two transcripts initiate 136 and 140 bases upstream from the first ATG codon in all human multidrug-resistant cell lines. The mdr1 gene is expressed in human normal kidney cells and HepG2 liver cells as a poly(A)+ RNA which starts from the same sites. Less prominent transcripts were found to initiate 155-180 bases upstream from the first ATG codon in vinblastine- or adriamycin-selected cell lines and 480-630 bases upstream in colchicine-selected cell lines. Southern hybridization analyses with different portions of a full-length cDNA indicate that the human mdr1 gene encompasses at least 70 kilobases of DNA amplified in all highly multidrug-resistant cell lines.

Original languageEnglish (US)
Pages (from-to)505-508
Number of pages4
JournalJournal of Biological Chemistry
Volume262
Issue number2
StatePublished - Mar 26 1987

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation'. Together they form a unique fingerprint.

  • Cite this

    Ueda, K., Clark, D. P., Chen, C. J., Roninson, I. B., Gottesman, M. M., & Pastan, I. (1987). The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation. Journal of Biological Chemistry, 262(2), 505-508.