TNFa 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. TNFa also exerts proliferation
by p38 activation, or when TRAF-2 simultaneously
induces the transcription factor NF-kB 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-kB.
NIK also may activate NF-kB.
The aim of the present article was to evaluate the
different components of this TNFa/IL-1 transduction
pathway in human prostate carcinoma (PC) in
comparison with normal human prostate. In prostate
cancer, pro-apoptotic TNFa/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-1a 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-kB.
In order to search a possible target to cancer prostate
treatment we proposed that inhibition of several
proinflamatory cytokines such as IL-1 and TNFa might
be a possible target for PC treatment, because decrease
the activity of all transduction pathway members that
activate transcription factors as NF-kB, Elk-1 or ATF-2