Heterogeneity of proteinkinase C activity and PKC-zeta expression in clinical breast carcinomas.
Proteinkinase C (PKC) is involved in carcinogenesis, proliferation, and metastatic spread of breast cancer. New anticancer strategies have been developed with PKC as a potential target for therapeutic intervention. However, most of the encouraging preliminary data were observed in breast cancer cell lines only. Insignificant information is available concerning clinical breast cancer cells. Our aim was to investigate the involvement of PKC in clinical breast carcinoma cells. To this end, we set up short-term cultures (3 days) of native tumor cells derived from 12 patients with advanced breast cancer. Addition of commonly used antineoplastics, including both single agents and combinations (tamoxifen, Adriamycin, paclitaxel, Adriamycin plus paclitaxel, epirubicin plus 4-OOH-cyclophosphamide, mitoxantrone, mitoxantrone plus vinorelbin, vinorelbin), simulated the clinical situation. In relation to each control we determined total PKC activity and quantified the PKC-zeta isoform. In 6 patients, no obvious alteration of PKC activities was detected. In the remainder, either inhibition or augmentation of PKC activity in the presence of cytostatics was detected. However, no tendency could be observed concerning the influence of the therapeutics on PKC activity. PKC-zeta expression was much more heterogeneous than activity assays. Although anticancer drugs influenced PKC-zeta expression, the results showed no uniformity with regard to PKC-zeta expression. Moreover, PKC-zeta expression did not correlate with total PKC activity, indicating a differential expression of different PKC isoenzymes. Therefore, we conclude that both PKC activity and PKC-zeta expression differ individually. More data concerning this topic are necessary prior to offering a clinically useful PKC-tailored regimen.
Schöndorf
T
T
Department of Gynecology and Obstetrics, University of Cologne, Germany. thomas.schoendorf@medizin.uni-koeln.de
Kurbacher
C M
CM
Becker
M
M
Warm
M
M
Kolhagen
H
H
Göhring
U J
UJ
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010693:Phloretin / Q000494:pharmacology; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010693:Phloretin; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta