Lack of influence of c-Ha-ras expression on the drug sensitivity of human bladder cancer histocultured in three-dimensions.
The mechanism of drug resistance in human cancers is complex. In addition to overexpression of a series of multiple-drug-resistance genes, there has been the suggestion that the Ha-ras gene may participate in conferring resistance. In this study, a series of three human-bladder carcinoma cell lines were studied, one parental type, one transfected by wild-type Ha-ras and another transfected by mutant Ha-ras. The ras gene was overexpressed in the latter two cell lines which also were more invasive than the parental when injected as individual cells in the nude-mouse bladder. The results described here have indicated that the ras-gene expression level or mutational status did not affect drug resistance when the tumor lines were histocultured as three-dimensional tissue on collagen-sponge-gels. The drug-response spectrum of the histocultured lines qualitatively reflected a clinical experience although all lines were relatively drug resistant, possibly reflecting their three-dimensional configuration in culture.
Theodorescu
D
D
University of Toronto, Department of Surgery, Ontario, Canada.
Connors
K M
KM
Groce
A
A
Hoffman
R M
RM
Kerbel
R S
RS
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003609:Dactinomycin / Q000627:therapeutic use / Q000633:toxicity; D004351:Drug Resistance / Q000235:genetics*; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use / Q000633:toxicity; D016296:Mutagenesis; D009368:Neoplasm Transplantation; D013936:Thymidine / Q000378:metabolism; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D014750:Vincristine / Q000627:therapeutic use / Q000633:toxicity
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D003609:Dactinomycin; D016685:Mitomycin; D014750:Vincristine; D002945:Cisplatin; D013936:Thymidine