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恶性和良性前列腺组织粗针活检中类固醇5α-还原酶2的差异基因表达

Differential gene expression of steroid 5 alpha-reductase 2 in core needle biopsies from malignant and benign prostatic tissue.

作者信息

Bjelfman C, Söderström T G, Brekkan E, Norlén B J, Egevad L, Unge T, Andersson S, Rane A

机构信息

Department of Clinical Pharmacology, University Hospital, Uppsala, Sweden.

出版信息

J Clin Endocrinol Metab. 1997 Jul;82(7):2210-4. doi: 10.1210/jcem.82.7.4080.

Abstract

Androgens are implicated in the development of prostate cancer (CAP) and benign prostate hyperplasia. The conversion of testosterone to the more potent metabolite dihydrotestosterone by prostatespecific steroid 5 alpha-reductase type 2 (5 alpha-red2) is a key mechanism in the action of androgens in the prostate and is important in the promotion and progression of prostate diseases. Manipulation of the turnover of androgens is thus fundamental in the pharmacological treatment strategy. We have developed a sensitive solution hybridization method for quantification of the gene expression of 5 alpha-red2 in core needle biopsies of the prostate. The 5 alpha-red2-specific messenger RNA (mRNA) levels were measured in 50 human prostate transrectal ultrasound-guided core biopsies obtained from 31 outpatients (median age 72, range 67-88 yr) undergoing biopsy for diagnostic purposes. Significant differences were observed in the gene expression of 5 alpha-red2 between cancerous and noncancerous tissue. In the 14 biopsies judged cancerous, the median 5 alpha-red mRNA levels were 3.5 amol/ng total RNA compared with 12.0 amol/ng total RNA in the biopsies showing no cancer (P = 0.0018). The median 5 alpha-red2 mRNA level in noncancerous tissue was thus 3.4 times higher than in the cancerous specimens.

摘要

雄激素与前列腺癌(CAP)和良性前列腺增生的发生有关。睾酮通过前列腺特异性类固醇5α-还原酶2型(5α-red2)转化为活性更强的代谢产物双氢睾酮,这是雄激素在前列腺中发挥作用的关键机制,对前列腺疾病的促进和进展具有重要意义。因此,调节雄激素的代谢周转是药物治疗策略的基础。我们开发了一种灵敏的溶液杂交方法,用于定量前列腺粗针活检组织中5α-red2的基因表达。在50例经直肠超声引导下的前列腺粗针活检组织中检测了5α-red2特异性信使核糖核酸(mRNA)水平,这些活检组织取自31例因诊断目的接受活检的门诊患者(中位年龄72岁,范围67 - 88岁)。在癌组织和非癌组织之间观察到5α-red2基因表达存在显著差异。在14例判定为癌的活检组织中,5α-red mRNA的中位水平为3.5 amol/ng总RNA,而在无癌的活检组织中为12.0 amol/ng总RNA(P = 0.0018)。因此,非癌组织中5α-red2 mRNA的中位水平比癌组织标本高3.4倍。

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