Expression of senescence-associate beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia
Expression of senescence-associate beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia
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DOI：
10.1016/s0090-4295(00)00538-0
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发表时间：
2000-07-01
期刊：
影响因子：
2.1
通讯作者：
Benson, MC
中科院分区：
文献类型：
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作者：
Choi, J;Shendrik, I;Benson, MC
目的。细胞衰老被认为是一种与衰老过程密切相关的独特细胞反应途径。衰老表型的特征是细胞对增殖和凋亡刺激的反应能力丧失，即便其正常代谢活动和活力得以维持。近期，一种新的生物标志物——衰老相关β - 半乳糖苷酶（SA - β - gal）被发现可用于识别具有衰老表型的细胞。在本研究中，我们检测了人类前列腺上皮细胞在长期培养后是否呈现衰老相关表型，并分析了一系列人类良性前列腺增生（BPH）标本，以确定细胞衰老过程是否可能是BPH发展的一个因素。
方法。从根治性前列腺切除术标本的外周区正常组织建立上皮细胞原代培养，并连续传代直至衰老。在根治性前列腺切除术或经直肠超声引导下活检后获取43例人类前列腺标本。对培养的细胞和组织标本进行组织化学染色，以显示细胞衰老生物标志物SA - β - gal的表达。
结果。正如其他类型培养细胞所报道的那样，人类前列腺上皮细胞在长期培养时表现出细胞衰老标志物SA - β - gal的广泛表达。在我们对肥大的人类前列腺组织的调查中，所分析的43例标本中有17例（40%）对SA - β - gal呈阳性染色。在这些组织中，仅在上皮细胞中观察到SA - β - gal的表达。未发现患者供体的实际年龄与SA - β - gal表达之间存在统计学相关性（P = 0.42）。然而，发现前列腺重量较高（大于55克）与SA - β - gal生物标志物的表达密切相关（P = 0.0001）。
结论。培养的前列腺上皮细胞在体外达到复制性衰老时表达SA - β - gal。对人类BPH标本中衰老标志物的调查显示，前列腺重量大于55克的BPH患者的前列腺上皮细胞表达SA - β - gal，而前列腺重量小于55克的BPH患者的前列腺往往缺乏衰老上皮细胞。基于这些结果，我们提出衰老上皮细胞的积累可能在与BPH相关的前列腺增大的发展中起作用。《泌尿学》56: 160 - 166, 2000。（C）2000，爱思唯尔科学公司
Objectives. Cellular senescence is a unique cellular response pathway thought to be closely associated with the aging process. The senescent phenotype is characterized by the loss of a cell's ability to respond to proliferative and apoptotic stimuli even while normal metabolic activity and vitality is maintained. Recently, a novel biomarker, senescent-associated beta-galactosidase (SA-beta-gal), was found to identify cells with the senescent phenotype. In the present study, we examined whether human prostatic epithelial cells adopt a senescence-associated phenotype after prolonged culture and analyzed a series of human benign prostatic hyperplasia (BPH) specimens to determine whether the cellular senescence process might be a factor in the development of BPH.Methods. A primary culture of epithelial cells was established from the normal tissue of the peripheral zone of a radical prostatectomy specimen and was serially passaged until senescence. Forty-three human prostate specimens were obtained subsequent to radical prostatectomy or transrectal ultrasound-guided biopsy. The cultured cells and tissue specimens were histochemically stained to reveal the expression of SA-beta-gal, the cellular senescence biomarker.Results. As has been reported for other types of cultured cells, human prostatic epithelial cells demonstrated widespread expression of the cellular senescence marker, SA-beta-gal, on prolonged culture. In our survey of hypertrophied human prostate tissues, 17 specimens (40%) of the 43 analyzed demonstrated positive staining for SA-beta-gal. In these tissues, SA-beta-gal expression was noted only in the epithelial cells. No statistical correlation (P = 0.42) between the chronologic age of the patient donor and SA-beta-gal expression was found. However, a high prostate weight (greater than 55 g) was found to correlate strongly with the expression of the SA-beta-gal biomarker (P = 0.0001).Conclusions. Cultured prostatic epithelial cells expressed SA-beta-gal on reaching replicative senescence in vitro. The survey of human BPH specimens for the senescent marker showed that prostatic epithelial cells in patients with BPH with more advanced enlargement of the prostate (greater than 55 g prostate weight) expressed SA-beta-gal, and the prostates from patients with BPH that weighed less than 55 g tended to lack senescent epithelial cells. On the basis of these results, we propose that the accumulation of senescent epithelial cells may play a role in the development of the prostatic enlargement associated with BPH. UROLOGY 56: 160-166, 2000. (C) 2000, Elsevier Science Inc.