MESSENGER-RNA EXPRESSION OF RESISTANCE PROTEINS AND RELATED FACTORS IN HUMAN OVARIAN-CARCINOMA CELL-LINES RESISTANT TO DOXORUBICIN, TAXOL AND CISPLATIN

Doxorubicin- (OAW-dox, SK-OV-dox), taxol- (OAW-tax, SK-OV-tax) and cis platin- (SK-OV-cis) resistant cells derived from the parental OAW-42 a nd SK-OV-3 cell lines were established. OAW-42 sublines showed high re sistance, the SK-OV-3 sublines only low resistance. OAW-42 sublines sh owed a cross-resistance profile typical of multidrug resistance (MDR). The sublines of SK-OV-3 showed a cross-resistance profile different f rom the OAW-42 sublines. The mRNA expression of several resistance pro teins and related factors was analyzed. An overexpression of P-glycopr otein 170 (P-170), glutathione-S-transferase-pi (GST-pi), thymidylate synthase (TS), glutathione peroxidase (GP) and c-jun was found in OAW- dox and OAW-tax cells. Additionally, OAW-tax cells expressed a higher mRNA level of protein kinase C beta 2. DNA analysis revealed a 2-fold gene amplification of P-170, whereas the genes for GST-pi TS and GP we re not amplified. SK-OV-dox and SK-OV-tax cells showed a decreased lev el of histone 3 (H3) and TS mRNA. This shows that the sublines of OAW- 42 developed resistance by co-expression of several resistance-related proteins and proto-oncogenes whereas the sublines of SK-OV-3 expresse d resistance by decreased expression of the proliferation-dependent pr oteins H3 and TS.