Gene rearrangement: A novel mechanism for MDR-1 gene activation Journal Article
| Authors: | Mickley, L. A.; Spengler, B. A.; Knutsen, T. A.; Biedler, J. L.; Fojo, T. |
| Article Title: | Gene rearrangement: A novel mechanism for MDR-1 gene activation |
| Abstract: | Drug resistance, a major obstacle to cancer chemotherapy, can be mediated by MDR-1/P-glycoprotein. Deletion of the first 68 residues of MDR-1 in an adriamycin-selected cell line after a 4;7 translocation, t(4q;7q), resulted in a hybrid mRNA containing sequences from both MDR-1 and a novel chromosome 4 gene. Further selection resulted in amplification of a hybrid gene. Expression of the hybrid mRNA was controlled by the chromosome 4 gene, providing a model for overexpression of MDR-1. Additional hybrid mRNAs in other drug-selected cell lines and in patients with refractory leukemia, with MDR-1 juxtaposed 3' to an active gene, establishes random chromosomal rearrangements with overexpression of hybrid MDR-1 mRNAs as a mechanism of acquired drug resistance. |
| Keywords: | cancer chemotherapy; human tissue; gene deletion; mutation; doxorubicin; polymerase chain reaction; neoplasms; in situ hybridization, fluorescence; drug resistance; tumor cells, cultured; gene activation; gene expression regulation, neoplastic; gene rearrangement; amino acid sequence; molecular sequence data; rna, messenger; dna, neoplasm; chromosome rearrangement; base sequence; translocation, genetic; dna primers; colon carcinoma; antibiotics, antineoplastic; rna, neoplasm; p-glycoprotein; drug resistance, multiple; chromosome 4; chromosomes, human, pair 4; chromosomes, human, pair 7; genes, mdr; gene rearrangements; humans; human; priority journal; article; mdr-1; hybridization, genetic |
| Journal Title: | Journal of Clinical Investigation |
| Volume: | 99 |
| Issue: | 8 |
| ISSN: | 0021-9738 |
| Publisher: | American Society for Clinical Investigation |
| Date Published: | 1997-04-15 |
| Start Page: | 1947 |
| End Page: | 1957 |
| Language: | English |
| PUBMED: | 9109439 |
| PROVIDER: | scopus |
| PMCID: | PMC508019 |
| DOI: | 10.1172/JCI119362 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
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