Prostate-associated gene 4 (PAGE4) protects cells against stress by elevating p21 and suppressing reactive oxygen species production.
Prostate-associated gene 4 (PAGE4) protects cells against stress by elevating p21 and suppressing reactive oxygen species production.
复制标题
前列腺相关基因 4 (PAGE4) 通过升高 p21 和抑制活性氧的产生来保护细胞免受压力。
DOI：
--
复制
发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Kulkarni Prakash
中科院分区：
文献类型：
--
作者：
Zeng Yu;Gao Dong;Kim John J;Shiraishi Takumi;Terada Naoki;Kakehi Yoshiyuki;Kong Chuize;Getzenberg Robert H;Kulkarni Prakash
背景
现在人们广泛认识到，氧化应激与前列腺良性和恶性疾病的风险之间存在很强的相关性。前列腺相关基因4（PAGE 4）是一种癌症/睾丸抗原（CTA），先前显示在前列腺癌（PCa）中上调，与组织学良性前列腺增生（BPH）相反，有症状。然而，其在这些疾病中的功能作用尚未完全了解。
方法
从8名PCa患者的PCa组织中分离的细胞类型中检测PAGE 4的mRNA水平。在前列腺疾病组织微阵列中分析PAGE 4蛋白表达谱。通过pCMV-PAGE 4-GFP转染过表达PAGE 4，并使用WST-1测定法测定细胞活力。
结果
PAGE 4的表达是高度动态的;虽然其表达在胎儿前列腺中非常高，但在正常成人前列腺中显著降低，但在有症状的BPH和PCa中都上调。然而，在患病的前列腺中，PAGE 4在炎性萎缩（PIA）病变的上皮细胞中高度表达，暗示PAGE 4的潜在应激反应功能。与这种作用一致，当前列腺癌（PCa）细胞系用各种应激因子（包括促炎细胞因子TNFα）处理时，PAGE 4蛋白水平上调。有趣的是，在受到应激挑战的细胞中，PAGE 4蛋白向线粒体的易位增加，活性氧的产生受到抑制。此外，p21在PAGE 4过表达细胞中以p53非依赖性方式升高，这导致细胞周期进展受阻，减轻应激诱导的DNA损伤，并减少细胞死亡。
结论
PAGE 4可能通过发挥应激保护和抗凋亡作用而促进PCa的发展。
BACKGROUND
It is now widely recognized that there is a strong correlation between oxidative stress and the risk of benign and malignant diseases of the prostate. Prostate-associated gene 4 (PAGE4) is a Cancer/Testis Antigen (CTA) that was previously shown to be up-regulated in prostate cancer (PCa) and symptomatic as opposed to histologic benign prostatic hyperplasia (BPH). However, its functional role in these diseases is not fully understood.
METHODS
The mRNA level of PAGE4 was detected in isolated cell types in PCa tissues that were obtained from 8 men with PCa. PAGE4 protein expression profile was analyzed in a prostate disease tissue microarray. PAGE4 was overexpressed by pCMV-PAGE4-GFP transfection and cell viability was determined using the WST-1 assay.
RESULTS
PAGE4 expression is highly dynamic; while its expression is very high in fetal prostate it is drastically decreased in the normal adult prostate but is up-regulated both in symptomatic BPH and PCa. However, in the diseased prostate, PAGE4 is highly expressed in the epithelial cells of Proliferative Inflammatory Atrophy (PIA) lesions alluding to a potential stress response function of PAGE4. Consistent with such a role, PAGE4 protein levels are up-regulated when prostate cancer (PCa) cell lines are treated with various stress factors including the proinflammatory cytokine TNFα. Interestingly, in cells challenged with stress there is increased translocation of the PAGE4 protein to the mitochondrion and production of reactive oxygen species is suppressed . Furthermore, p21 is elevated in a p53-independent manner in PAGE4-overexpressing cells which results in impeded cell cycle progression, attenuated stress-induced DNA damage, and decreased cell death.
CONCLUSIONS
PAGE4 may be contributing to the development of PCa by playing a stress-protective and anti-apoptotic role.
登录
查看更多内容
影响因子：
5
作者：
Schenk, Jeannette M.;Kristal, Alan R.;Thompson, Ian M.
通讯作者：
Thompson, Ian M.
DOI：
10.1016/j.ajpath.2012.06.040
发表时间：
2012-10
期刊：
The American journal of pathology
影响因子：
--
作者：
N. Sampson;C. Ruiz;C. Zenzmaier;L. Bubendorf;P. Berger
通讯作者：
N. Sampson;C. Ruiz;C. Zenzmaier;L. Bubendorf;P. Berger
DOI：
10.1111/j.1749-6632.2002.tb04068.x
发表时间：
2002-01-01
期刊：
NITRIC OXIDE: NOVEL ACTIONS, DELETERIOUS EFFECTS AND CLINICAL POTENTIAL
影响因子：
--
作者：
Espey, MG;Miranda, KM;Wink, DA
通讯作者：
Wink, DA
影响因子：
11.2
作者：
Kumar, Binod;Koul, Sweaty;Koul, Hari K.
通讯作者：
Koul, Hari K.
影响因子：
7.4
作者：
Shiraishi T;Terada N;Zeng Y;Suyama T;Luo J;Trock B;Kulkarni P;Getzenberg RH
通讯作者：
Getzenberg RH