Title |
Mutant p53 expression enhances drug resistance in a hepatocellular carcinoma cell line
|
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Published in |
Cancer Chemotherapy and Pharmacology, March 2004
|
DOI | 10.1007/s00280-004-0767-4 |
Pubmed ID | |
Authors |
Kin-Tak Chan, Maria Li Lung |
Abstract |
Chemoresistance is a major problem in the treatment of hepatocellular carcinoma. Certain p53 mutants may enhance drug resistance in cancer cells. To determine whether two frequently occurring p53 mutants, R248Q and R273C, would increase the drug resistance of liver cancer cells, stable cell lines expressing these specific p53 mutants were established by transfecting the p53-null Hep3B cells with mutant p53 expression vectors, and then treating them with the anticancer drugs doxorubicin and paclitaxel. The cells expressing the p53 mutant, R248Q, but not R273C, displayed cross-resistance to both drugs, in contrast to the control cells expressing the vector alone. Moreover, both the expression and the activity of the multiple drug resistance gene product, P-glycoprotein, were elevated in p53 mutant R248Q-expressing cells. Reduced uptake of doxorubicin was also observed in the R248Q-expressing cells. These results suggest that expression of the p53 mutant, R248Q, in liver cancer cells may enhance their drug resistance and that upregulation of P-glycoprotein activity may contribute to this protective effect. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 37 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 10 | 27% |
Student > Bachelor | 6 | 16% |
Researcher | 5 | 14% |
Student > Doctoral Student | 3 | 8% |
Professor > Associate Professor | 2 | 5% |
Other | 2 | 5% |
Unknown | 9 | 24% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 8 | 22% |
Biochemistry, Genetics and Molecular Biology | 7 | 19% |
Medicine and Dentistry | 7 | 19% |
Immunology and Microbiology | 2 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
Other | 2 | 5% |
Unknown | 10 | 27% |