Genes amplified and overexpressed in human multidrug-resistant cell lines Journal Article
| Authors: | Van der Bliek, A. M.; Baas, F.; Van der Velde-Koerts, T.; Biedler, J. L.; Meyers, M. B.; Ozols, R. F.; Hamilton, T. C.; Joenje, H.; Borst, P. |
| Article Title: | Genes amplified and overexpressed in human multidrug-resistant cell lines |
| Abstract: | Multidrug resistance (MDR) is associated with overproduction of Mr170,000 membrane proteins (P-glycoproteins) caused by either gene amplification, transcriptional activation, or both. In rodents the amplified domain comprises genes that encode P-glycoproteins and at least five unrelated genes, one of which encodes the calcium-binding protein sorcin. The amplification and increased expression of these genes always includes one P-glycoprotein-encoding gene (pgpl in hamsters, homologous to mdrl in humans). In human MDR cells only elevated mdrl expression has been shown thusfar, although another P-glycoprotein encoding gene (mdr3, homologous to hamster pgp3) is closely linked. Here we show that the human homolog of the hamster sorcin gene resides on chromosome 7 like the P-glycoprotein-encoding genes. Furthermore, gene classes designated 4, 5, and 6 are coamplified with mdrl and mdr3 in the human ovarian carcinoma cell line 2780AD, which strongly suggests that the overall structure of the human MDR domain is the same as in rodents. Class 6 was moderately and mdrl was highly overexpressed in this cell line. Four other human MDR cell lines also have much higher mdrl overexpression than expected from the relatively low levels (2- to 30-fold) of gene amplification. This contrasts with the results of previous work with rodent MDR cells, in which the increase in P-glycoprotein mRNA levels usually parallels the increase in gene copy number. Although four of the five human MDR cell lines have coamplified mdr3, its expression was undetectable. Our results confirm the central role of the mdrl (pgpl) gene in MDR and suggest that different cross-resistance patterns are not due to differential expression of different P-glycoprotein genes. © 1988, American Association for Cancer Research. All rights reserved. |
| Keywords: | human cell; doxorubicin; gene amplification; gene expression; vincristine; drug resistance; tumor cells, cultured; gene expression regulation; species specificity; cell culture; rna, messenger; membrane glycoproteins; tumor cell line; daunorubicin; dactinomycin; calcium-binding proteins; p-glycoprotein; colchicine; human; priority journal; support, non-u.s. gov't; support, u.s. gov't, p.h.s. |
| Journal Title: | Cancer Research |
| Volume: | 48 |
| Issue: | 21 |
| ISSN: | 0008-5472 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1988-11-01 |
| Start Page: | 5927 |
| End Page: | 5932 |
| Language: | English |
| PUBMED: | 2901906 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 6 August 2020 -- Source: Scopus |
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