Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends on MEK/ERK activation
| العنوان: | Cisplatin-induced apoptosis in human malignant testicular germ cell lines depends on MEK/ERK activation |
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| المؤلفون: | O Meschter, A Fayyazi, Stefan Schweyer, N Miosge, Heinz-Joachim Radzun, F. Zschunke, Paul Thelen, Thilo Schlott, Afsaneh Soruri, A. Heintze |
| المصدر: | British Journal of Cancer |
| بيانات النشر: | Nature Publishing Group, 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Male, MAPK/ERK pathway, Cancer Research, MAP Kinase Signaling System, Urology, Blotting, Western, cisplatin, Antineoplastic Agents, Mitogen-activated protein kinase kinase, 03 medical and health sciences, 0302 clinical medicine, Testicular Neoplasms, TGCT, Tumor Cells, Cultured, medicine, Humans, Experimental Therapeutics, Phosphorylation, Protein kinase A, Caspase, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, Mitogen-Activated Protein Kinase Kinases, Cisplatin, 0303 health sciences, biology, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Kinase, Gene Expression Profiling, Cell Cycle, apoptosis, Neoplasms, Germ Cell and Embryonal, Cell cycle, Genes, p53, Testicular germ cell, MEK, 3. Good health, ERK, Oncology, Apoptosis, 030220 oncology & carcinogenesis, biology.protein, Cancer research, business, Signal Transduction, medicine.drug |
| الوصف: | Testicular germ cell tumours (TGCT) represent the most common malignancies in young males. Whereas in 1970s, the survival rate in patients with metastatic testicular tumours was only 5%, these days, 80% of the patients treated by modern chemotherapy will survive their disease. The drug that revolutionised the cure rate for patients with metastatic testicular tumours was cisdiamminedichloroplatinum (cisplatin, CDDP). In vitro experiments on neoplastic germ cell lines showed that their exquisite sensitivity to CDDP could be attributed to p53-dependent and -independent pathways. Applying cDNA macroarray, semiquantitative RT-PCR and Western blot analyses, blocking experiments, caspase activity assays, and morphological methods, we sought here to define the p53-independent pathway(s) involved in the CDDP-induced apoptosis. For this purpose, we used the human TGCT cell line NCCIT, the mutated p53 of which is known to remain inactive during the course of CDDP-induced apoptosis. Our experiments showed that within hours of CDDP application, two prototype members of the 'mitogen-activated protein kinase' (MAPK) family, designated 'MAPK ERK kinase' (MEK) and 'extracellular signal-regulated kinase' (ERK), were dually phosphorylated and caspase-3 became active. Functional assays using MEK inhibitors demonstrated that the phosphorylation of MEK and ERK was required for the activation of caspase-3 as the executing caspase. Interestingly, experiments with the human malignant germ cell line NTERA, which is known to possess wild-type p53, revealed the same results. Thus, our data suggest that CDDP mediates its p53-independent apoptosis-inducing effect on the malignant human testicular germ cells--at least partially--through activation of the MEK-ERK signalling pathway. July 2004 |
| اللغة: | English |
| تدمد: | 1532-1827 0007-0920 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c22ebe65af98cb161b290a48c0f9ee6c http://europepmc.org/articles/PMC2409982 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c22ebe65af98cb161b290a48c0f9ee6c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15321827 00070920 |
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