The three major mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK are signal transducers involved in a broad range of cell functions including survival, apoptosis, and cell differentiation. Whereas JNK and p38 have been generally linked to cell death and tumor suppression, ERK plays a prominent role in cell survival and tumor promotion, in response to a broad range of stimuli such as cytokines, growth factors, ultraviolet radiation, hypoxia, or pharmacological compounds. However, there is a growing body of evidence supporting that JNK and p38 also contribute to the development of a number of malignances. In this paper we focus on the involvement of the MAPK pathways in prostate cancer, including the less-known ERK5 pathway, as pro- or antitumor mediators, through their effects on apoptosis, survival, metastatic potential, and androgen-independent growth.

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BackgroundIn this study was investigate IAPs in normal human prostate (NP), benign prostatic hyperplasia (BPH), prostatic intraepithelial neoplasia (PIN) and prostatic carcinoma (PC), and their involvement in apoptosis/proliferation via NF-kB (TNF-α, IL-1) stimulation.MethodsImmunohistochemical and Western blot analyses were performed in 10 samples of normal prostates, 35 samples of BPH, 27 samples diagnosis of PIN (with low-grade PIN or high-grade PIN) and 95 samples of PC (with low, medium or high Gleason grades).ResultsIn NP, cytoplasm of epithelial cells were positive to c-IAP1/2 (80% of samples), c-IAP-2 (60%), ILP (20%), XIAP (20%); negative to NAIP and survivin. In BPH, epithelial cells were immunostained to c-IAP1/2 (57.57%), c-IAP-2 (57.57%), ILP (66.6%), NAIP (60.6%), XIAP (27.27%), survivin (9.1%). Whereas low-grade PIN showed intermediate results between NP and BPH; results in high-grade PIN were similar to those found in PC. In PC, epithelial cells were immunostained to c-IAP1/2, c-IAP-2, ILP, NAIP, XIAP (no Gleason variation) and survivin (increasing with Gleason).ConclusionsIAPs could be involved in prostate disorder (BPH, PIN and PC) development since might be provoke inhibition of apoptosis and subsequently cell proliferation. At the same time, different transduction pathway such as IL-1/NIK/NF-kB or TNF/NF-kB (NIK or p38) also promotes proliferation. Inhibitions of IAPs, IL-1α and TNFα might be a possible target for PC treatment since IAPs are the proteins that inhibited apoptosis (favour proliferation) and IL-1α and TNFα would affect all the transduction pathway involucrate in the activation of transcription factors related to survival or proliferation (NF-kB, Elk-1 or ATF-2).

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