Topoisomerase I gene expression and cell sensitivity to camptothecin in human cell lines of different tumor types.
Topoisomerase I (topo I) gene expression and cell sensitivity to camptothecin were investigated in seven human cancer cell lines not selected in vitro for drug resistance. The cell lines were of different tumor origin, and included two ovarian carcinomas (A2780 and IGROV-1), a cervix squamous cell carcinoma (A431), an osteosarcoma (U2-OS), a glioblastoma (GBM) and two different clones of a malignant melanoma (665/2/60 and 665/2/21). Topo I gene expression was evaluated by Northern blotting analysis and cell sensitivity to camptothecin was determined using the colony-forming assay after a 1 h exposure to the drug. A wide range of drug sensitivity levels was found among the examined cell lines. Cell doubling times and distribution in cell cycle phases were not correlated with camptothecin cytotoxicity. In particular, the percent of untreated cells in S phase was not predictive of the drug sensitivity. No correlation was found between level of topo I gene expression and cell response to camptothecin. These results indicate that the level of topo I expression is not the only critical determinant of cell sensitivity to camptothecin in unselected human cancer cell lines. Therefore, topo I gene expression may not be a useful predictive parameter of tumor response.
Perego
P
P
Division of Experimental Oncology B, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Capranico
G
G
Supino
R
R
Zunino
F
F
D015152:Blotting, Northern; D002166:Camptothecin / Q000494:pharmacology*; D004264:DNA Topoisomerases, Type I / Q000032:analysis*; D004351:Drug Resistance; D015870:Gene Expression; D006801:Humans; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D004264:DNA Topoisomerases, Type I; D002166:Camptothecin