TNF-α/IL-1/NF-κB transduction pathway in human cancer prostate
TNFα exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2008 |
| País: | España |
| Institución: | Universidad de Alcalá (UAH) |
| Repositorio: | e_Buah Biblioteca Digital Universidad de Alcalá |
| Idioma: | inglés |
| OAI Identifier: | oai:ebuah.uah.es:10017/32678 |
| Acceso en línea: | http://hdl.handle.net/10017/32678 https://dx.doi.org/10.14670/HH-23.1279 |
| Access Level: | acceso abierto |
| Palabra clave: | Prostate carcinoma IL-1 TNF-α NF-κB NIK p38 Antineoplastic Agents/therapeutic use Apoptosis Cell Proliferation Cell Survival Humans Interleukin-1/antagonists & inhibitors Interleukin-1/metabolism Male NF-kappa B/metabolism Prostatic Neoplasms/drug therapy Prostatic Neoplasms/metabolism Prostatic Neoplasms/pathology Protein-Serine-Threonine Kinases/metabolism Signal Transduction/drug effects Transcription Factor AP-1/metabolism Tumor Necrosis Factor-alpha/antagonists & inhibitors Tumor Necrosis Factor-alpha/metabolism p38 Mitogen-Activated Protein Kinases/metabolism Biología Genética Ciencia Biology Genetics Science |
| Sumario: | TNFα exerts apoptosis throughout an intracellular transduction pathway that involves the kinase proteins TRAF-2 (integration point of apoptotic and survival signals), ASK1 (pro-apoptotic protein), MEK-4 (p38 activator and metastasis suppressor gene), JNK (stress mitogen activated protein kinase) and the transcription factor AP-1. TNFα also exerts proliferation by p38 activation, or when TRAF-2 simultaneously induces the transcription factor NF-κB by NIK. NIK and p38 may also be activated by IL-1. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-κB. NIK also may activate NF-κB. The aim of the present article was to evaluate the different components of this TNFα/IL-1 transduction pathway in human prostate carcinoma (PC) in comparison with normal human prostate. In prostate cancer, pro-apoptotic TNFα/AP-1 pathway is probably inactivated by different factors such as p21 (at ASK-1 level) and bcl-2 (at JNK level), or diverted towards p38 or NIK activation. IL-1α enhances proliferation through IL-1RI that activates either NIK or p38 transduction pathway. P38 and NIK activate different transcription factors related with cell proliferation and survival such as ATF-2, Elk-1 or NF-κB. In order to search a possible target to cancer prostate treatment we proposed that inhibition of several proinflamatory cytokines such as IL-1 and TNFα might be a possible target for PC treatment, because decrease the activity of all transduction pathway members that activate transcription factors as NF-κB, Elk-1 or ATF-2. |
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