The purpose of the work described in this thesis was to investigate the effects of upregulation of c-erbB-2 by cDNA transfection and the downregulation by ribozyme transfection on chemotherapeutic drug sensitivity, in vitro invasion, and expression of a range of mRNA and proteins. Four novel multidrug resistant variants of the human breast carcinoma cell line, MDAMB- 435S-F, were established by pulse selection with taxol or adriamycin. In vitro toxicity tests revealed that the taxol resistant variants, MDA-MB-435S-F/Taxol-10p and MDA-MB-435S-F/Taxol-10p4p were significantly more resistant to taxol, with crossresistance to vincristine and taxotere, but not to adriamycin, carboplatin, etoposide or 5-fluorouracil. Adriamycin accumulation studies revealed that both variants displayed increased adriamycin efflux. P-glycoprotein and possibly topoisomerases, but not mrpl, mrp2, mrp4, mrp5, DHFR, thymidylate synthase or GST n, were found to play a role in taxol resistance. MDA-MB-435S-F cells were resistant to adriamycin selection. MDA-MB-435S-F/AdrlOp gained no significant increase in resistance to adriamycin following 10 rounds of exposure to adriamycin, although it did become resistant to VP-16 and was sensitised to vincristine and 5-fluorouracil. MDA-MB-435S-F/Adr-10pl0p was slightly resistant to adriamycin, VP-16, taxotere and vincristine. It was sensitised to taxol, 5-fluorouracil and carboplatin. P-glycoprotein, mrpl, mrp2, mrp4 and mrp5 were not altered at the mRNA level in the adriamycin selected variants. Reduced adriamycin accumulation appears to be the mechanism by which MDA-MB-435S-F/Adr-10pl0p became slightly resistant to adriamycin. Drug selection induced c-erbB-1 expression at protein but not mRNA level in MDAMB-435S-F. C-erbB-3 protein levels fell dramatically after drug selection. Drug selection of MDA-MB-435S-F induced more aggressively invasive cell lines, as defined by the gain of an ability to invade and relocate. This is a novel discovery for this thesis. The aggressive two-staged invasive phenotype appears to be linked to decreased adhesion and motility and perhaps c-erbB-1 induction and c-erbB-3 repression, but not to increased secretion of a range of proteases. C-erbB-2 was not found to play a role.