Ex vivo assays to evaluate the role of protein kinase C in tumor cells of patients with breast cancer.
New anti-cancer strategies have been developed with respect to proteinkinase C (PKC) as a potential target for therapeutic intervention in patients with advanced breast cancer. Using cell lines, most of the preliminary data are encouraging but insufficient information is available concerning clinical breast cancer cells. Thus, we decided to clarify the involvement of PKC in clinical breast carcinoma cells. We isolated viable tumor cells from fluids or tissue burden of eleven patients with advanced breast cancer. Performance of short term cultures supplemented with commonly used antineoplastics mimicked the clinical situation. We determined the ex vivo chemosensitivity pattern of each cell population. Additionally, we analysed total PKC activity and quantified the PKC-isoform eta. All assays showed a heterogeneous highly variable distribution of the data investigated. No tendency could be observed regarding the influence of the therapeutics on PKC activity, PKC-eta expression or chemoresistance, respectively. Moreover, changes in neither PKC-eta expression, PKC activity nor chemoresistance induced by a particular drug in an individual tumor necessarily predicted the same reaction in another tumor to this agent. Therefore, we concluded that more explorative data concerning this topic are required prior to the development of a clinically useful therapy regimen with PKC as the major target.
Schöndorf
T
T
Department of Gynecology and Obstetrics, University of Cologne, Kerpener Strasse 34, D-50931 Cologne, Germany.
Becker
M
M
Kolhagen
H
H
Kurbacher
C M
CM
Göhring
U J
UJ
D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000502:physiology*; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured; D000099221:Protein Kinase C zeta
D000970:Antineoplastic Agents; D007527:Isoenzymes; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta