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Article: Mutant p53 expression enhances drug resistance in a hepatocellular carcinoma cell line

TitleMutant p53 expression enhances drug resistance in a hepatocellular carcinoma cell line
Authors
Issue Date2004
PublisherSpringer. The Journal's web site is located at http://www.springer.com/medicine/oncology/journal/280
Citation
Cancer Chemotherapy And Pharmacology, 2004, v. 53 n. 6, p. 519-526 How to Cite?
AbstractChemoresistance 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. © Springer-Verlag 2004.
Persistent Identifierhttp://hdl.handle.net/10722/150797
ISSN
2015 Impact Factor: 2.824
2015 SCImago Journal Rankings: 1.283
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, KTen_US
dc.contributor.authorLung, MLen_US
dc.date.accessioned2012-06-26T06:10:38Z-
dc.date.available2012-06-26T06:10:38Z-
dc.date.issued2004en_US
dc.identifier.citationCancer Chemotherapy And Pharmacology, 2004, v. 53 n. 6, p. 519-526en_US
dc.identifier.issn0344-5704en_US
dc.identifier.urihttp://hdl.handle.net/10722/150797-
dc.description.abstractChemoresistance 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. © Springer-Verlag 2004.en_US
dc.languageengen_US
dc.publisherSpringer. The Journal's web site is located at http://www.springer.com/medicine/oncology/journal/280en_US
dc.relation.ispartofCancer Chemotherapy and Pharmacologyen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCarcinoma, Hepatocellular - Genetics - Metabolism - Pathologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Survival - Drug Effectsen_US
dc.subject.meshDna, Neoplasm - Analysisen_US
dc.subject.meshDoxorubicin - Metabolism - Pharmacologyen_US
dc.subject.meshDrug Resistance, Neoplasm - Geneticsen_US
dc.subject.meshFlow Cytometryen_US
dc.subject.meshGene Expression Regulation, Neoplasticen_US
dc.subject.meshHumansen_US
dc.subject.meshIn Situ Nick-End Labelingen_US
dc.subject.meshLiver Neoplasms - Genetics - Metabolism - Pathologyen_US
dc.subject.meshMutationen_US
dc.subject.meshP-Glycoprotein - Metabolismen_US
dc.subject.meshPaclitaxel - Metabolism - Pharmacologyen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTumor Suppressor Protein P53 - Genetics - Metabolismen_US
dc.subject.meshUp-Regulationen_US
dc.titleMutant p53 expression enhances drug resistance in a hepatocellular carcinoma cell lineen_US
dc.typeArticleen_US
dc.identifier.emailLung, ML:mlilung@hku.hken_US
dc.identifier.authorityLung, ML=rp00300en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1007/s00280-004-0767-4en_US
dc.identifier.pmid15004724-
dc.identifier.scopuseid_2-s2.0-2542424899en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-2542424899&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume53en_US
dc.identifier.issue6en_US
dc.identifier.spage519en_US
dc.identifier.epage526en_US
dc.identifier.isiWOS:000221344600009-
dc.publisher.placeGermanyen_US
dc.identifier.scopusauthoridChan, KT=7406034062en_US
dc.identifier.scopusauthoridLung, ML=7006411788en_US

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