title: Paclitaxel/Taxol sensitivity in human renal cell carcinoma is not determined by the p53 status.
abstract: In this study, we analyzed the role of the p53 status for paclitaxel/Taxol sensitivity in renal cell carcinomas (RCCs) of the clear cell type. Using immunohistochemistry, nuclear p53 accumulation could not be correlated to the paclitaxel/Taxol sensitivity. DNA sequencing detected a p53 gene mutation in two out of eight RCC cell lines, i.e. in exon 8 (cell line clearCa-6), and in exon 9 (cell line clearCa-5). No correlation, however, was found between the p53 status of our RCC cell lines and their paclitaxel/Taxol sensitivity as indicated by the IC50 values. However, paclitaxel-induced growth inhibition in paclitaxel-sensitive RCC cell lines was accompanied by an increase in apoptosis, irrespective of their p53 status. Although CD95 up-regulation was observed in renal cell carcinoma with wild-type p53 upon paclitaxel treatment, paclitaxel-induced apoptosis itself is triggered independently from the CD95 system. In conclusion, the p53 status cannot predict paclitaxel/Taxol sensitivity in RCC cell lines of the clear cell type.
authors.affiliation: Institute of Pathology, Heinrich-Heine-University, Moorenstr. 5, D-40225 Düsseldorf, Germany. reinecke@med.uni-duesseldorf.de
authors.forename: Petra
authors.initials: P
authors.lastname: Reinecke
authors.forename: Thomas
authors.initials: T
authors.lastname: Kalinski
authors.forename: Csaba
authors.initials: C
authors.lastname: Mahotka
authors.forename: Michael
authors.initials: M
authors.lastname: Schmitz
authors.forename: Marion
authors.initials: M
authors.lastname: Déjosez
authors.forename: Helmut Erich
authors.initials: HE
authors.lastname: Gabbert
authors.forename: Claus Dieter
authors.initials: CD
authors.lastname: Gerharz
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm; D019008:Drug Resistance, Neoplasm; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D017239:Paclitaxel