Apoptosis profiles in benign prostatic hyperplasia: Close associations of cell kinetics with percent area density of histologic composition

Zhang, Xianghua; Zhang, Qian; Zhang, Zheng; Na, Yan-qun; Guo, Yinglu

doi:10.1016/j.urology.2006.05.013

Cited by 20 publications

(14 citation statements)

References 21 publications

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“…We observed that most of the replicating epithelial cells were basal cells in contrast to malignant prostatic lesions in which luminal as well as basal cells proliferate (21). Moreover, the observed increase in expression of the antiapoptotic factor, Bcl-2 in BPH may also account for accumulation of cells (22,23). The question then shifts to the origin of the accumulated cells.…”

Section: Discussionmentioning

confidence: 78%

A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

Alonso-Magdalena

Brössner

Reiner

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

150

127

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Benign prostatic hyperplasia (BPH) is usually described as a pathological proliferation of prostatic fibroblasts/myofibroblasts and epithelial cells. In the present study of BPH samples, we have made a morphological and immunohistochemical study of BPH prostatic sections using markers of proliferation, apoptosis, hormone receptors, and TGF-␤ signaling. We found no evidence of proliferation in the stroma but in the epithelium of some ducts; 0.7% of the basal and 0.4% of luminal cells were positive for Ki67 and PCNA. Androgen receptor and estrogen receptor beta (ER␤)1 and ER␤cx were abundant in both stromal and epithelial compartments but cells expressing ER␣ were very rare. What was very common in all BPH samples was the following: (i) regions of the ductal epithelium where the epithelial cells did not express E-cadherin, had lost their polarization, and become spindle shaped (the nuclei of these cells were strongly positive for pSmad 3 and Snail); and (ii) regions where the walls of the blood vessels were extremely thick and there was loss of endothelial layer. Loss of E-cadherin, increased pSmad 3, and high expression of Snail are all characteristic of epithelial-mesenchymal transition (EMT). We conclude that BPH is not a disease of prostatic stromal proliferation but rather of accumulation of mesenchymal-like cells derived from the prostatic epithelium and the endothelium. TGF-␤ is thought to play a key role in EMT. Our data suggests that TGF-␤/Smad should be considered as targets for treatment of BPH.proliferation ͉ TGF beta signaling

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Section: Discussionmentioning

confidence: 78%

A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

Alonso-Magdalena

Brössner

Reiner

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

150

127

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“…Bax inhibits Bcl-2 function and allows the cell to enter the death program [12]. Caspase-3 is a member of the caspase family of cysteine proteases which is central to the cell death pathway, as the extrinsic and intrinsic cell death pathways converge to activate this protein for the final execution of apoptosis [14]. Activation of caspase-3 is primarily responsible for the cleavage of poly (adenosine diphosphate-ribose) polymerase (PARP).…”

Section: Introductionmentioning

confidence: 99%

Expression of apoptosis-regulating genes in the rat prostate following botulinum toxin type a injection

et al. 2012

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BackgroundOnabotulinumtoxin A (OnabotA) injection has been investigated as a novel treatment for benign prostatic enlargement caused by benign prostatic hyperplasia. An OnabotA - induced volume reduction caused by sympathetic fibers impairment has been proposed as a potential mechanism of action. Our aim was to investigate the expression of apoptosis-regulating proteins in the rat prostate following OnabotA intraprostatic injection.MethodsAdult Wistar rats were injected in the ventral lobes of the prostate with 10 U of OnabotA or saline. A set of OnabotA-injected animals was further treated with 0.5 mg/kg of phenylephrine (PHE) subcutaneously daily. All animals were sacrificed after 1 week and had their prostates harvested. Immunohistochemical staining was performed for Bax, Bcl-xL and caspase-3 proteins and visualized by the avidin-biotin method. The optical density of the glandular cells was also determined, with measurement of differences between average optical densities for each group.ResultsSaline-treated animals showed intense epithelial staining for Bcl-xL and a faint labelling for both Bax and Caspase-3. OnabotA-treated rats showed a reduced epithelial staining of Bcl-xL and a consistently increased Bax and Caspase-3 staining when compared with saline-treated animals. PHE-treated animals showed a stronger Bcl-xL staining and reduced staining of both Bax and Caspase-3 when compared to the OnabotA group. Mean signal intensity measurements for each immunoreaction confirmed a significant decrease of the signal intensity for Bcl-xL and a significant increase of the signal intensity for Bax and Caspase 3 in OnabotA-injected animals when compared with the control group. In OnabotA+PHE treated animals mean signal intensity for Bcl-xL, Bax and Caspase 3 immunoreactions was identical to that of the control animals.ConclusionsThese results support the hypothesis that OnabotA activates apoptotic pathways in the rat prostate through a mechanism that involves sympathetic outflow impairment.

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“…In normal prostatic tissue, Bcl-2 and caspase-3 expression in epithelial cells was either undetectable or only weakly detected. Therefore, it was suggested that lowering apoptosis rate in BPH may be associated with alterations in the balance between Bcl-2 and caspase-3 (20). Bcl-2 is an inner mitochondrial membrane protein, and its predominant effect is to prolong cell survival by inhibiting apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Musulju improves benign prostatic hyperplasia by regulating inflammatory and apoptotic proteins

Chung

Cheon

et al. 2016

Molecular Medicine Reports

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Alternative medicine is a widely accepted therapeutic approach for the management of various diseases. The Korean medicine, musulju (MSJ), has been traditionally used to improve vital energy in men with reduced physical strength and a weakened urinary system. The present study determined the mechanisms underlying the protective effect of MSJ against benign prostatic hyperplasia (BPH), a common disorder in elderly men that involves inflammation-mediated imbalance between cell proliferation and death. MSJ treatment was demonstrated to decrease prostate weight, cell proliferation, and the protein expression of proliferating cell nuclear antigen in a rat model of BPH. In addition, MSJ markedly reduced serum testosterone levels, 5α-reductase2 mRNA expression and BPH-associated upregulation of inflammatory proteins, inducible nitric oxide synthase and cyclooxygenase 2. Furthermore, MSJ induced apoptosis by regulating B-cell lymphoma (Bcl)-2 protein expression and the Bcl-2:Bax ratio, leading to caspase 3 activation. Taken together, MSJ demonstrated antiproliferative effects in BPH model rats by regulating the expression levels of proteins involved in inflammation and apoptosis. The effects of MSJ may be attributed to its alternative therapeutic properties.

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Apoptosis profiles in benign prostatic hyperplasia: Close associations of cell kinetics with percent area density of histologic composition

Cited by 20 publications

References 21 publications

A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

A role for epithelial-mesenchymal transition in the etiology of benign prostatic hyperplasia

Expression of apoptosis-regulating genes in the rat prostate following botulinum toxin type a injection

Musulju improves benign prostatic hyperplasia by regulating inflammatory and apoptotic proteins

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