title: P-glycoprotein expression in multidrug-resistant human ovarian carcinoma cell lines.
abstract: Multiple selections with either vinblastine or vincristine in the human ovarian carcinoma cell line SKOV3 resulted in variants with increasing degrees of multidrug resistance. SKOV3 derivatives that span a wide range in resistance (4- to 2000-fold) were obtained and analyzed for P-glycoprotein expression. In general, we observed a progressive increase in P-glycoprotein level (detected by Western blot) that paralleled the increase in multidrug resistance. However, a more detailed analysis of the P-glycoprotein mRNA and gene level indicated that the amount of P-glycoprotein expressed may be under complex control. At low levels of resistance, only an increase in P-glycoprotein mRNA and protein was observed. At intermediate to high levels of resistance P-glycoprotein gene amplification became evident. At the high level of resistance, an example was observed where only the amount of P-glycoprotein was increased without a concomitant increase in mRNA or gene copy. The mechanisms through which the content of P-glycoprotein in the plasma membrane is mediated are not understood; it is possible that the resistant variants identified here represent perturbations at different levels of regulation.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, Toronto, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Bradley
authors.forename: M
authors.initials: M
authors.lastname: Naik
authors.forename: V
authors.initials: V
authors.lastname: Ling
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002277:Carcinoma / Q000032:analysis* / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000032:analysis* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D014750:Vincristine