Induction of drug resistance and protein kinase C genes in A2780 ovarian cancer cells after incubation with antineoplastic agents at sublethal concentrations.
We examined the inducibility of drug resistance (MDR1, MRP1, LRP) and protein kinase C (PKC) isozyme (alpha, epsilon, eta, theta, tau, zeta) corresponding genes in A2780 ovarian cancer cells after a 24-hour treatment with adriamycin (ADR), camptothecin (CAM), etoposide (ETO) or vincristine (VCR). Sublethal concentrations of drugs were used to exclude short-term effects caused by selection. Cell cycle analysis was performed to identify possible correlation between resistance factors, PKC isozymes and proliferation. We found a mostly combined induction of MDR1, LRP, PKC tau and PKC zeta by CAM, ETO and VCR. PKC alpha, epsilon, eta and theta gene expression altered variably. Cell cycle analysis showed that A2780 cells responded with a marked G2/M arrest after a 24-hour treatment with CAM, ETO and VCR but an association between the induction of PKC isozymes corresponding genes and proliferation was not seen. Our analysis points to a possible link between atypical PKC tau/PKC zeta and MDR1/LRP in cytostatic stress response of cancer cells.
Brügger
Dorothee
D
Department of Pediatric Haematology/Oncology, Hoppe-Seyler Str. 1, D-72076 Tübingen, Germany.
Brischwein
Klaus
K
Liu
Chao
C
Bader
Peter
P
Niethammer
Dietrich
D
Gekeler
Volker
V
Beck
James F
JF
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis / Q000235:genetics; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002166:Camptothecin / Q000009:adverse effects / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000009:adverse effects / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005047:Etoposide / Q000009:adverse effects / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019450:Genes, MDR; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D011493:Protein Kinase C / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured; D020394:Vault Ribonucleoprotein Particles / Q000096:biosynthesis / Q000235:genetics; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D002166:Camptothecin; D004317:Doxorubicin; D005047:Etoposide; D007527:Isoenzymes; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D011493:Protein Kinase C; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C421109:multidrug resistance-associated protein 1