An investigation of the role of the ErbB receptor family in chemotherapeutic drug resistance and invasion in human breast cancer

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