TNF-α/IL-1/NF-κB transduction pathway in human cancer prostate
AuthorsPaniagua Gómez-Álvarez, Ricardo; Royuela García, María del Mar; Fraile Laiz, Benito; Rodríguez Berriguete, Gonzalo
IdentifiersPermanent link (URI): http://hdl.handle.net/10017/32678
Sercrisma International S.L.
AffiliationUniversidad de Alcalá. Departamento de Biomedicina y Biotecnología. Unidad docente Biología Celular y Genética
Ministerio de Educación y Ciencia
Histology and Histopathology. 2008, v. 23, n. 10, p. 1279-1290
SAF2007-61928 (Ministerio de Educación y Ciencia)
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
© Sercrisma International S.L., 2008
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.