Title |
p53 Pathway in Renal Cell Carcinoma Is Repressed by a Dominant Mechanism
|
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Published in |
Cancer Research, March 2004
|
DOI | 10.1158/0008-5472.can-03-1541 |
Pubmed ID | |
Authors |
Katerina V. Gurova, Jason E. Hill, Olga V. Razorenova, Peter M. Chumakov, Andrei V. Gudkov |
Abstract |
Renal cell carcinoma (RCC) rarely acquires mutations in p53 tumor suppressor gene, suggesting that p53 signaling in this tumor type might be repressed by some other mechanism. In fact, all four RCC-derived cell lines we tested maintained wild-type p53 but were not capable of transactivating p53-responsive reporters and endogenous p53-responsive genes. p53 protein in RCC showed normal response to genotoxic stress, including accumulation, nuclear translocation, and activation of specific DNA binding. Functional and expression analysis of Mdm2, MdmX, and Arf showed lack of involvement of these p53 regulators in the observed defect of p53 function in RCC. However, activation of p53-mediated transactivation could be achieved by extremely high levels of p53 attained by lentivirus vector-driven transduction, suggesting the involvement of a dominant inhibitor in repression of p53-dependent transactivation in RCC. Consistently, p53 inactivation prevailed in the hybrids of RCC cells with the cells possessing fully functional p53. Remarkably, cells of normal kidney epithelium also caused partial p53 repression in cell fusion experiments, suggesting that RCC-specific p53 repression may be based on an unknown dominant mechanism also acting in normal kidney tissue. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 1 | 2% |
Ukraine | 1 | 2% |
Canada | 1 | 2% |
Unknown | 43 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 13 | 28% |
Researcher | 7 | 15% |
Student > Master | 6 | 13% |
Student > Bachelor | 4 | 9% |
Professor | 4 | 9% |
Other | 7 | 15% |
Unknown | 5 | 11% |
Readers by discipline | Count | As % |
---|---|---|
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Biochemistry, Genetics and Molecular Biology | 8 | 17% |
Social Sciences | 2 | 4% |
Nursing and Health Professions | 1 | 2% |
Other | 1 | 2% |
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