Abstract
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).
Highlights
In this study was investigate inhibitor of apoptosis proteins (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-a, IL-1) stimulation
Positive immunostaining to c-IAP-1/2 was observed in the cytoplasm of epithelial cells in 80% of normal prostates patients, in 57.57% of patients with BPH, 59.25% of patients with PIN and in more 60% of PC patients (Table 1)
Optic density to c-IAP-1/2 was similar in the four groups (NP, BPH, PIN and PC)
Summary
In 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-a, IL-1) stimulation. IAPs family comprises eight proteins: Survivin, XIAP (ILP-1), c-IAP-1, c-IAP-2, NAIP, ILP-2, apollon (BRUCE) and ML-IAP (LIVIN). C-IAP-1 and c-IAP-2 proteins are broadly expressed in normal human tissues with a cytoplasmic diffuse location pattern. Several authors suggest that the expression of these proteins is associated with biological characteristic of cancer such as apoptosis [7] or aged-related [8]. The coding sequence of ILP-2 (IAP-like protein 2) [11] is very similar to that of XIAP (ILP-1), with 80% identity at the amino acid level [12]. Northern blot and RT-PCR analysis of both embryonic and adult human tissues reveals that ILP-2 expression is restricted to testis [13]. Overexpression of ILP-2 had no protective effect on death induced by bax or caspase 9 [11,12]
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