Profiling of signaling molecules in four different human prostate carcinoma cell lines before and after induction of apoptosis.
We have treated four prostate tumor cell lines, DU-145, PC-3, LNCaP and 22RV1 with various concentrations of cisplatin in order to check for influence on viability and for onset of apoptosis induction. At a cisplatin concentration of 20 microM, 22RV1 and DU-145 cells showed approximately 22% and 18% and PC-3 and LNCaP cells showed approximately 4 and 10% dead cells, respectively. When checking for apoptosis induction, the differences among the cell lines became even more evident. DU-145 and 22RV1 cells showed apoptosis induction at 5- and 2-microM cisplatin, whereas in the case of LNCaP and PC-3 cells comparable apoptosis induction was observed at 100-microM cisplatin; hence, the difference between the two groups of cell lines with respect to apoptosis induction is 20- and 50-fold, respectively. We used 37 antibodies to screen the expression levels of key signaling molecules and their phosphorylation status where appropriate. DU-145 and PC-3 cells are androgen-receptor negative and harbor non-functional p53, whereas LNCaP and 22RV1 cells are androgen-receptor positive and harbor wild-type p53. The results of the profiling of DU-145 and PC-3 support the notion that an intact PTEN/AKT pathway (as found in DU-145 and 22RV1 cells) and the presence of active p38 are responsible for the high sensitivity to apoptosis induction and that neither the androgen receptor nor the p53 status is of primary importance for the differences observed with respect to apoptosis induction.
Skjøth
Iben H E
IH
Institute for Biochemistry & Molecular Biology, University of Southern Denmark, 5230 Odense, Denmark.
Issinger
Olaf-Georg
OG
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D011944:Receptors, Androgen / Q000032:analysis / Q000502:physiology; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin