Rent level of androgen dependence. NEP and ET-1 are inversely and
Rent level of androgen dependence. NEP and ET-1 are inversely and directly related to an activated state of the NFB/proteasome pathway, respectively. A combination therapy targeting both pathways may ultimately prove to be of benefit in clinical practice.Background The 26S proteasome is part of the ubiquitin-proteasome system (UPS) and constitutes a large multiprotein complex present in all cells, both PubMed ID: in the cytoplasm and nucleus, which degrades ubiquitinated proteins. The proteasome targets proteins that are damaged, oxidised or misfolded. Furthermore, it orchestrates the orderly degradation of regulatory proteins that govern cell cycle, transcription factor activation, apoptosis, and cell trafficking [1,2].* Correspondence: [email protected] 1 Department of Medical Oncology, University Hospital of Larissa, Larissa, Greece Full list of author information is available at the end of the articleThe activation of the nuclear factor kappa B (NFB), a key transcription factor, is dependent on proteasomemediated degradation of the inhibitory protein IBa [3]. Thereby, the proteasome regulates the transcriptional activity of NFB. NFB induces expression of cell adhesion molecules (i.e., E-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1), prosurvival proteins (i.e., Bcl-2), and growth factors, like interleukin-6 (IL-6), thus promoting cell survival, angiogenesis, and metastasis, related to cancer progression and resistance to chemotherapy in various solid tumors, including PC [2,4]. Neutral endopeptidase 24.11 (NEP, neprilysin, enkephalinase, CALLA, CD10, EC is a thermolysin-like zink metallopeptidase of the M13 family that is normally?2011 Patrikidou et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Patrikidou et al. Cancer Cell International 2011, 11:13 2 ofexpressed by numerous tissues, including prostate. This enzyme is an integral plasma membrane ectopeptidase that plays an important role in turning off peptide signalling events at the cell surface. It cleaves peptide bonds on the amino side of hydrophobic amino acids and inactivates a variety of physiologically active peptides, including atrial natriuretic factor, substance P, bradykinin, oxytocin, Leuand Met-enkephalins, neurotensin, endothelin, bombesin, and bombesin-like peptides, which are collectively termed neuropeptides (NPs) [5-8]. NEP reduces the local concentration of NP available for receptor binding and signal transduction via G-protein receptor coupling. It has been implicated in controlling cellular proliferation by hydrolysing NPs such as endothelin and bombesin-like peptides, found to be potent mitogens for both benign and malignant cells [9,10]. Loss or decrease in NEP expression has been reported in a variety of malignancies, including PC [11]. order GSK1363089 Reduced NEP allows PubMed ID: an accumulation of higher peptide concentrations at the cell surface and may facilitate the development and progression of neoplasia [7,12]. The aberration of the NFB/UPS pathway and the NEP/NPs axis have been independently linked to the development and progression of PC [2,13-17]. In this work we have hypothesised that both increased NP signalling as a result of NEP loss a.

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