Analysis of Vitamin A-related receptors expression in prostate cancer

前列腺癌中维生素A相关受体表达分析

• 批准号: 11671549
• 负责人: WATANABE Masatoshi
• 金额: $ 2.3万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671549/
• 关键词: Prostate cancer; Vitamin A-related receptors; methylation; 前立腺; レチノイド

1. Immunohistochemical analysis of Vitamin A related receptors in human prostates : Expression of retinoic acid receptor (RAR)-α, β, γ, retinoid X receptor (RXR)-α, β, and γ was analyzed in formalin-fixed paraffin-embedded tissue sections from 15 patients with benign prostatic hyperplasia (BPH) and 15 with prostate cancer (PCa) using each polyclonal antibody. RARs-α and γ were detected in all BPH and PCa samples, RXRs-α and γ in all BPH samples and 80% of PCa samples, RXR-β in 13% of both samples, and RAR-β in all BPH and 13% of PCa samples. 2.Analysis of Vitamin A related receptor mRNAs in human prostates : A nonradioactive mRNA in situ hybridization technique using digoxigenin-labeled probe for RAR-α, β, γ were analyzed in five BPH and five PCa samples. RAR-α, and γ mRNA were detected in all BPH and PCa samples while RAR-β not detected. Thus, RAR-β mRNA was examined by RT-PCR in the microdisected samples, showing that 20% of PCa and 80% of BPH samples had RAR-β mRNA.3. Analysis of regulation in RAR-β2 gene expression in human prostates : Regulation mechanisms of RAR-β2 gene were analyzed because PCa showed dramatically decreasing expression of RAR-β gene. (1) PCR-SSCP analysis showed no abnormal band in 10 PCa samples, suggesting that there may be no mutation in any exons of the RAR-β gene. (2) Using bisulfite PCR methods, methylation status was analyzed within the RAR-β promoter region. Aberrant methylation was detected in 83% of the 24 PCa samples while no methylation in BPH samples. These results suggest that one of Vitamin A related receptors, RAR-β, especially β2 may play an important role in carcinogenesis of the prostate, and the possibility that this gene may become a tumor marker or a target for gene therapy.

1.人前列腺中维生素A相关受体的免疫组织化学分析：使用每种多克隆抗体，在来自15名良性前列腺增生（BPH）和15名前列腺癌（PCa）患者的福尔马林固定石蜡包埋组织切片中分析视黄酸受体（RAR）-α、β、γ，类维生素A X受体（RXR）-α、β和γ的表达。所有前列腺增生和前列腺癌样本中均检测到RAR-α和γ，所有前列腺增生样本和80%的前列腺癌样本中均检测到RXR-α和γ，两种样本中均检测到RXR-β，所有前列腺增生和13%的前列腺癌样本中均检测到RAR-β。2.人前列腺中维生素A相关受体mRNA的分析：采用地高辛标记的RAR-α、β、γ探针，采用非放射性mRNA原位杂交技术，分析了5例BPH和5例PCa中的RAR-α、β、γ。BPH和PCa组织中RAR-α、γ mRNA表达阳性，RAR-β mRNA表达阴性。RT-PCR检测到20%的PCa和80%的BPH组织中存在RAR-β mRNA. RAR-β2基因在前列腺组织中的表达调控分析：前列腺癌组织中RAR-β2基因的表达明显降低，因此我们分析了RAR-β2基因的调控机制。(1)PCR-SSCP分析显示，10例PCa标本均未出现异常条带，提示RAR-β基因的任何一个外显子可能均未发生突变。(2)使用亚硫酸氢盐PCR方法，分析RAR-β启动子区域内的甲基化状态。在24例PCa标本中，83%的标本存在异常甲基化，而在BPH标本中未发现异常甲基化。提示维生素A相关受体RAR-β，尤其是β2在前列腺癌的发生中可能起重要作用，该基因有可能成为肿瘤标志物或基因治疗的靶点。

项目成果

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K.Fukutome、M.Watanabe、M.Murata、H.Uemura、Y.Kubota、J.Kawamura、H.Ito 和 R.Yatani.：“N-乙酰转移酶 1 遗传多态性影响前列腺癌发生的风险。”癌症

Fukutome K et al.: "N-acetyl transferase 1 genetic polymorphisms influence the risk of prostate cancer development."Cancer Letters. 136. 83-87 (1999)

Fukutome K 等人：“N-乙酰转移酶 1 基因多态性影响前列腺癌发展的风险。”《癌症快报》。

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Ueda T 等人：“与人类前列腺癌相关的 13 个基因上常见缺失的 ul-cM 区域的鉴定”基因，染色体癌症。

Watanabe M et al.: "Comparative study of the incidence of prostate cancer in Japan rersus the United States : A Review"Ural Oncology. 5. 274-283 (2000)

Watanabe M 等人：“日本与美国前列腺癌​​发病率的比较研究：综述”乌拉尔肿瘤学。