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The fragile equilibrium between proliferation and apoptosis maintains the size and normal homeostasis of each organ. Apoptosis increase in BPH might be an attempt to inhibit the enhanced cell proliferation, although this attempt seems to be insufficient to develop massive apoptosis. Several authors have reported the increasing of survival and several proliferation factors (bcl-2, NF-κB and p21) that inhibit apoptotic, but also several cytokines such as TNFα and IL-1. TNFα induces death or cell proliferation by activation of NF-kB, also activated by IL-1α. Binding of TNFα/TNFRI complex to TRADD proteins activates TRAF-2. TRAF-2 activation might stimulate two different pathways. One is initiated by TRAF-2 and NIK, interaction that activates NF-κB (nuclear factor-κB). The other pathway activates the cascade ASK1, which activate the transcription factor AP-1. TNFα and IL-1 also exert proliferation by p38 activation. P38 activated several transcription factors such as Elk-1, ATF-2 and NF-κB. The aim of the present article was to evaluate the different components of this TNFα/IL-1 transduction pathway in benign prostate hyperplasia (BPH) in comparison with normal human prostate. Our previous results showed that in BPH the percentages of immunostained specimens and the intensity of immunoreactions to TRAF-2, ASK-1, MEK-4, JNK, p- Elk-1, ATF-2 decreased respect normal prostate; immunoreactions to IL-1β, IL-1Ra Ikkα/β, IkBα, p-IkB and NF-kB (p50) increased respect normal prostate; no variations has been observed to TNFα, TNF-RI, IRAK, TRAF-6, NIK; and, IL-1α, IL-1RI, IL-1RII, α-PAK, MEK-6, AP-1 and NF-kB (p65) were positive in BPH samples (expression not observed in normal prostate). In BPH, proliferation is triggered by IL-1 (NF-KB, ATF-2 or Elk-1) and in part counteracted by TNF-α/AP-1 pathway, which promotes apoptosis. BPH is a heterogeneous disease in which multiple transduction pathways may interact in the uncontrolled apoptosis/cell proliferation. Since IL-1 and TNFα are related to inflammation, inhibition of these cytokines might be a possible target for BPH treatment, because decrease the activity of all transduction pathway members that activate transcription factors as AP-1, NF-kB, Elk-1 or ATF-2.



Book title

Horizons in Cancer Research

Publication Date





235 - 247