Mutations of TP53 do not correlate with the sensitivity to paclitaxel--a study using 27 gynaecological cancer cell lines.
The correlation between inactivation of the TP53 gene through mutation or the presence of high-risk human papillomavirus (HPV) DNA and intrinsic paclitaxel sensitivity was studied in 27 gynaecological cancer cell lines. IC(50) values, as a measure of drug sensitivity, were determined using a 96-well clonogenic assay. TP53 mutations were investigated with polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequencing. HPV status was studied with PCR using HPV consensus primers. TP53 mutations were found in 7/11 vulvar SCC cell lines. Only 2/9 endometrial and 1/7 ovarian cancer cell lines carried TP53 mutations. One vulvar and one endometrial cancer cell line were HPV-positive; both carrying HPV type-16 DNA. Thus, TP53 was functionally normal in 3/11 vulvar, 6/9 endometrial and 6/7 ovarian cancer cell lines. The IC(50) values for paclitaxel were 0.60-2.9, 0.49-2.3 and 0.40-3.4 nM in the vulvar, endometrial and ovarian cancer cell lines, respectively. No correlation could be demonstrated between inactivation of the TP53 gene and paclitaxel sensitivity in vitro; the cell lines were evaluated as one group or according to their anatomical origin or histology. Previous reports have given inconclusive results, partly due to the cell types used, i.e. normal, cancerous or transformed cells. Our results support the view that paclitaxel sensitivity of tumour-derived cancer cell lines is not related to the TP53 status.
Rantanen
V
V
Department of Gynecology, Turku City Hospital, Turku, Finland. virantanen@hotmail.com
Engblom
P
P
Raitanen
M
M
Hietanen
S
S
Haarala
M
M
Grénman
S
S
Syrjänen
S
S
D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D016158:Genes, p53; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D020128:Inhibitory Concentration 50; D009154:Mutation / Q000235:genetics*; D017239:Paclitaxel / Q000627:therapeutic use*; D030361:Papillomavirus Infections / Q000150:complications / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D018807:Polymorphism, Single-Stranded Conformational; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014412:Tumor Virus Infections / Q000150:complications / Q000235:genetics
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel