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 language | English (US) |
|---|---|
| Pages (from-to) | 505-508 |
| Number of pages | 4 |
| Journal | Journal of Biological Chemistry |
| Volume | 262 |
| Issue number | 2 |
| State | Published - 1987 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology