5α-reductase type 3 expression in human benign and malignant tissues: a comparative analysis during prostate cancer progression.
5α-reductase type 3 expression in human benign and malignant tissues: a comparative analysis during prostate cancer progression.
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DOI：
10.1002/pros.21318
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发表时间：
2011-07
期刊：
影响因子：
2.8
通讯作者：
Mohler, James L.
中科院分区：
文献类型：
--
作者：
Godoy, Alejandro;Kawinski, Elzbieta;Li, Yun;Oka, Daizo;Alexiev, Borislav;Azzouni, Faris;Titus, Mark A.;Mohler, James L.
关键词：
人5 α-类固醇还原酶的第三种同工酶5 α-还原酶-3在前列腺组织中在mRNA水平上被鉴定。然而，5 α-还原酶-3蛋白的表达水平及其在人体组织中的细胞定位仍然未知。开发、验证了特异性单克隆抗体，并首次使用免疫染色分析来表征5 α-还原酶-3蛋白在18种良性和26种恶性人体组织类型中的表达。在良性组织中，5 α-还原酶-3免疫染色在常规雄激素调节的人体组织中较高，如骨骼肌和前列腺。然而，在非常规雄激素调节的组织中也观察到高水平的表达，这表明雄激素的多个靶组织或5 α-还原酶-3在人体组织中的不同功能。在恶性组织中，5 α-还原酶-3免疫染色普遍存在，但与良性组织相比，在某些癌症中尤其过度表达，这表明5 α-还原酶-3作为恶性肿瘤生物标志物的潜在作用。在良性前列腺中，5 α-还原酶-3免疫染色定位于基底上皮细胞，在分泌/腔上皮细胞中未观察到免疫染色。在高级别前列腺上皮内瘤变（HGPIN）中，5 α-还原酶-3免疫染色定位于基底上皮细胞和HGPIN特征性的肿瘤上皮细胞。在雄激素刺激的和去势复发的前列腺癌（CaP）中，5 α-还原酶-3免疫染色存在于大多数上皮细胞中，并且处于相似的水平，并且高于良性前列腺中观察到的水平。分析5 α-还原酶-3在人体组织中的表达和功能可能有助于开发良性前列腺肥大的治疗方法和预防和治疗CaP。
A third isozyme of human 5α-steroid reductase, 5α-reductase-3, was identified in prostate tissue at the mRNA level. However, the levels of 5α-reductase-3 protein expression and its cellular localization in human tissues remain unknown. A specific monoclonal antibody was developed, validated, and used to characterize for the first time the expression of 5α-reductase-3 protein in 18 benign and 26 malignant human tissue types using immunostaining analyses. In benign tissues, 5α-reductase-3 immunostaining was high in conventional androgen-regulated human tissues, such as skeletal muscle and prostate. However, high levels of expression also were observed in non-conventional androgen-regulated tissues, which suggest either multiples target tissues for androgens or different functions of 5α-reductase-3 among human tissues. In malignant tissues, 5α-reductase-3 immunostaining was ubiquitous but particularly over-expressed in some cancers compared to their benign counterparts, which suggests a potential role for 5α-reductase-3 as a biomarker of malignancy. In benign prostate, 5α-reductase-3 immunostaining was localized to basal epithelial cells, with no immunostaining observed in secretory/luminal epithelial cells. In high-grade prostatic intraepithelial neoplasia (HGPIN), 5α-reductase-3 immunostaining was localized in both basal epithelial cells and neoplastic epithelial cells characteristic of HGPIN. In androgen-stimulated and castration-recurrent prostate cancer (CaP), 5α-reductase-3 immunostaining was present in most epithelial cells and at similar levels, and at levels higher than observed in benign prostate. Analyses of expression and functionality of 5α-reductase-3 in human tissues may prove useful for development of treatment for benign prostatic enlargement and prevention and treatment of CaP.
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DOI：
10.1073/pnas.0700420104
发表时间：
2007-05-15
影响因子：
11.1
作者：
Mahajan, Nupam P.;Liu, Yuanbo;Whang, Young E.
通讯作者：
Whang, Young E.
影响因子：
4.8
作者：
Godoy, Alejandro;Watts, Anica;Smith, Gary J.
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Smith, Gary J.
影响因子：
6.6
作者：
MIYAMOTO, KK;MCSHERRY, SA;MOHLER, JL
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MOHLER, JL
影响因子：
2.1
作者：
Eisenberger, MA;Laufer, M;Raghavan, D
通讯作者：
Raghavan, D
影响因子：
6.6
作者：
Ford, OH;Gregory, CW;Mohler, JL
通讯作者：
Mohler, JL