A p53-dominant transcriptional response to cisplatin in testicular germ cell tumor-derived human embyronal carcinoma

作者: Joanna S Kerley-Hamilton , Aimee M Pike , Na Li , James DiRenzo , Michael J Spinella

DOI: 10.1038/SJ.ONC.1208755

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摘要: Testicular germ cell cancers remain one of the few solid tumors routinely cured in advanced stages with conventional cisplatin-based chemotherapy. The mechanisms largely unknown. Through use gene-expression array profiling we define immediate transcriptional targets response to cisplatin testicular cell-derived human embryonal carcinoma cells. We report 46 genes upregulated and five repressed by cisplatin. Several these gene products, including FAS, TRAILR3, PHLDA3, LRDD, IER3 are previously implicated apoptotic death receptor pathway, while others SESN1, FDXR, PLK3, DDIT4 known mediators reactive oxygen species generation. Approximately 54% established or suspected downstream p53. Specific siRNA p53 prevents cisplatin-mediated activation pathway renders cells relatively resistant cytotoxicity. Interestingly, knockdown nearly entire set identified fail respond have a diminished cisplatin, suggesting that many new direct indirect GPR87, STK17A, INPP5D, FLJ11259, EPS8L2. data indicate robust is linked hypersensitivity Many products may participate unique curability this disease.

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