Abstract
Two out of three diseases of the prostate gland affect aging men worldwide. Benign prostatic hyperplasia (BPH) is a noncancerous enlargement affecting millions of men. Prostate cancer (PCa) in turn is the second leading cause of cancer death. The factors influencing the occurrence of BPH and PCa are different; however, in the course of these two diseases, the overexpression of heat shock proteins is observed. Heat shock proteins (HSPs), chaperone proteins, are known to be one of the main proteins playing a role in maintaining cell homeostasis. HSPs take part in the process of the proper folding of newly formed proteins, and participate in the renaturation of damaged proteins. In addition, they are involved in the transport of specific proteins to the appropriate cell organelles and directing damaged proteins to proteasomes or lysosomes. Their function is to protect the proteins against degradation factors that are produced during cellular stress. HSPs are also involved in modulating the immune response and the process of apoptosis. One well-known factor affecting HSPs is the androgen receptor (AR)—a main player involved in the development of BPH and the progression of prostate cancer. HSPs play a cytoprotective role and determine the survival of cancer cells. These chaperones are often upregulated in malignancies and play an indispensable role in tumor progression. Therefore, HSPs are considered as one of the therapeutic targets in anti-cancer therapies. In this review article, we discuss the role of different HSPs in prostate diseases, and their potential as therapeutic targets.
Highlights
The consequence of ligand-binding domain (LBD) binding to the ligand is a change in the androgen receptor (AR) conformation and its translocation to the cell nucleus, in which a dimer is formed that connects to ARE in the promoter region of the genes critical for the growth and development of a healthy prostate, as well as prostate cancer cells, and important factors for the terminal differentiation of PSA, or human kallikrein 2 [41]
The results of this study clearly show that the inhibition of HSP70 reduces the phosphorylation of YB-1 regulating the transcription of both AR-FL and AR-V7, which leads to a reduction in the expression level of the AR variants and an increase in the effectiveness of therapy in castration-resistant prostate cancer (CRPC)
The results of many studies suggest that there are a number of dynamic interactions between client proteins and the HSP40/HSP70/HSP90 chaperone machinery in prostate cancer cells, including CRPC, which is consistent with the pleiotropic nature of molecular chaperones
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Upon the detection of stress, HSF-1 becomes activated, detaches from the HSP and, by binding to the specific regions of DNA, the sequences of heat shock elements (HSEs) in the promoter region of HSP genes, activates protein transcription. The result of this process is an increase in the level of free HSPs, which in turn deactivates HSF-1 in response to a feedback response [7]. Prostate cancer cells are constantly exposed to proteotoxic stress This state forces the cell to activate the cytoprotective mechanisms, in which are involved, among others, heat shock proteins, which are a therapeutic target, including CRPC cancer [20]. Along with the increase in the incidence of BPH, the treatment options have increased, but they are still not fully satisfactory [22,23]
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