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Modulation of Activity of the Promoter of the Human MDR 1 Gene by Ras and p53
Abstract
Drug resistance in human cancer is associated with overexpression of the multidrug resistance ( MDR 1) gene, which confers cross-resistance to hydrophobic natural product cytotoxic drugs. Expression of the MDR 1 gene can occur de novo in human cancers in the absence of drug treatment. The promoter of the human MDR 1 gene was shown to be a target for the c-Ha-Ras-1 oncogene and the p53 tumor suppressor gene products, both of which are associated with tumor progression. The stimulatory effect of c-Ha-Ras-1 was not specific for the MDR 1 promoter alone, whereas a mutant p53 specifically stimulated the MDR 1 promoter and wild-type p53 exerted specific repression. These results imply that the MDR 1 gene could be activated during tumor progression associated with mutations in Ras and p53.
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Citations
Cited by
mdm2 expression is induced by wild type p53 activity.
Barak, Y., Juven, T., Haffner, R., & Oren, M. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05678.x · Cited by 1,290
When mutants gain new powers: News from the mutant p53 field
Brosh, R., & Rotter, V. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2693 · Cited by 1,132
Gain of function mutations in p53
Dittmer, D., Pati, S., Zambetti, G., Chu, S., Teresky, A. K., Moore, M., Finlay, C., & Levine, A. J. (1993) · Nature Genetics · doi:10.1038/ng0593-42 · Cited by 894
Role of p53 in Cell Death and Human Cancers
Ozaki, T., & Nakagawara, A. (2011) · Cancers · doi:10.3390/cancers3010994 · Cited by 650
GENETIC ANALYSIS OF THE MULTIDRUG TRANSPORTER
Gottesman, M. M., Hrycyna, C. A., Schoenlein, P. V., Germann, U. A., & Pastan, I. (1995) · Annual Review of Genetics · doi:10.1146/annurev.ge.29.120195.003135 · Cited by 478
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Metadata
- Authors
- Chin, K.-V., Ueda, K., Pastan, I., & Gottesman, M. M.
- Venue
- Science
- Published
- 1992-01-24
- Volume
- 255
- Issue
- 5043
- Pages
- 459-462
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2076149108
- Cited by
- 726
- References
- 0
- FWCI
- 28.88
- Type
- journal article
- Language
- en
- Open access
- closed
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- Chin, K.-V., Ueda, K., Pastan, I., & Gottesman, M. M. (1992). Modulation of Activity of the Promoter of the Human MDR 1 Gene by Ras and p53. Science. https://doi.org/10.1126/science.1346476
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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