HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

 

Review

TNF-α/IL-1/NF-κB transduction pathway in human cancer prostate

Mar Royuela, Gonzalo Rodríguez-Berriguete, Benito Fraile and Ricardo Paniagua

Department of Cell Biology and Genetics, University of Alcalá, Alcalá de Henares, Madrid, Spain.

Offprint requests to: Mar Royuela, Department of Cell Biology and Genetics, University of Alcalá, Alcalá de Henares, Madrid, Spain. e-mail: mar.royuela@uah.es


Summary. TNF
α 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 TNF
α/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 TNF
α 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. Histol Histopathol 23, 1279-1290 (2008)

Key words: Prostate carcinoma; IL-1, TNF-α, NF-κB, NIK, p38

DOI: 10.14670/HH-23.1279