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| MODULATION OF ACTIVITY OF THE PROMOTER OF THE HUMAN MDR1 GENE BY RAS AND P53 |
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| Author(s): CHIN KV, UEDA K, PASTAN I, GOTTESMAN MM |
| Source: SCIENCE Volume: 255 Issue: 5043 Pages: 459-462 Published: JAN 24 1992 |
| Times Cited: 680 References: 43 |
| Abstract: Drug resistance in human cancer is associated with overexpression of the multidrug resistance (MDR1) gene, which confers cross-resistance to hydrophobic natural product cytotoxic drugs. Expression of the MDR1 gene can occur de novo in human cancers in the absence of drug treatment. The promoter of the human MDR1 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 MDR1 promoter alone, whereas a mutant p53 specifically stimulated the MDR1 promoter and wild-type p53 exerted specific repression. These results imply that the MDR1 gene could be activated during tumor progression associated with mutations in Ras and p53. |
| Document Type: Article |
| Language: English |
Addresses:
1. NCI, CELL BIOL LAB, BLDG 37, ROOM 1B22, BETHESDA, MD 20892 USA
2. KYOTO UNIV, DEPT AGR CHEM, KYOTO 606, JAPAN
3. NCI, MOLEC BIOL LAB, BETHESDA, MD 20892 USA |
| Publisher: AMER ASSOC ADVANCEMENT SCIENCE, 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: HA590 |
| ISSN: 0036-8075 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |