LACK OF INFLUENCE OF C-HA-RAS EXPRESSION ON THE DRUG-SENSITIVITY OF HUMAN BLADDER-CANCER HISTOCULTURED IN 3-DIMENSIONS

The mechanism of drug resistance in human cancers is complex. In addit ion to overexpression of a series of multiple-drug-resistance genes, t here has been the suggestion that the Ha-ras gene may participate in c onferring resistance. In this study, a series of three human-bladder c arcinoma cell lines were studied, one parental type, one transfected b y wild-type Ha-ras and another transfected by mutant Ha-ras. The ras g ene was overexpressed in the latter two cell lines which also were mor e 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 re sistance when the tumor lines were histocultured as three-dimensional tissue on collagen-sponge-gels. The drug-response spectrum of the hist ocultured lines qualitatively reflected a clinical experience although all lines were relatively drug resistant, possibly reflecting their t hree-dimensional configuration in culture.