Study of the identification of new genes inducing hormone refractory prostate cancer

激素难治性前列腺癌新基因鉴定研究

• 批准号: 11470339
• 负责人: KUBOTA Yoshinobu
• 金额: $ 3.46万
• 依托单位: Yokohama City University Grant-in Aid for Scientific Research (B)(2)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470339/
• 关键词: Prostate cancer; Hormone Refractory; Differential Display; OSM-? gene; nmt55 gene; Liprin? gene; 再熱; 再燃現象; 遺伝子発現

In this research, new human genes associated with hormone refractory prostate cancer were tried to be identified by applying differential display PCR methodology. The RNA of human Prostate cancer and normal prostate tissue was analyzed for differentially expressed gene. We have clones more than one hundred possible genes. And OSM-? and nmt55 genes were identified as important genes.OSM-β gene is one of the tyrosine kinase type receptor family genes. This gene was shown to be highly expressed in hormone refractory prostate cancer and suggested to be involves in androgen independent growth characteristics.The nmt55 gene is coded as one of the transcriptional factors. We have shown that the expression of this gene was closely associated with the expression of androgen receptor. This gene was shown to be disappear last in hormone refractory prostate cancer and suggested to be associated with androgen independent growth regulation.We have also analyzed the RNA of LNCaP human prostate cancer cells treated with dihydrotestosterone for differentially expressed gene. Two important genes Liprin?-2 and NKx 3.1 like gene were cloned.Liprinα-2 gene expression was shown to be down-regulated by androgen and this gene might be associated with the induction of apoptosis after androgen deprivation. Since Liprinα-2 gene expression disappeared completely lost in androgen independent prostate cancer cell line (PC-3, DU-145) or hormone refractory prostate cancer tissues, this gene is suggested to play a roll in the induction of hormone independent prostate cells.

本研究试图通过差异显示聚合酶链式反应(Differential Display PCR)的方法，寻找与激素难治性前列腺癌相关的人类新基因。对前列腺癌和正常前列腺组织的RNA进行分析，寻找差异表达基因。我们已经克隆了一百多个可能的基因。和OSM-？OSM-β基因是酪氨酸激酶型受体家族基因之一。该基因在激素非依赖性前列腺癌中高表达，可能与雄激素非依赖性生长有关。nmt55基因编码为转录因子之一。我们已经证明该基因的表达与雄激素受体的表达密切相关。该基因在激素非依赖性前列腺癌中最后消失，提示与雄激素非依赖性生长调控有关。我们还分析了双氢睾酮处理的人前列腺癌LNCaP细胞的RNA差异表达基因。克隆了两个重要的基因Liprin？-2和NKx3.1-like基因，发现Liprinα-2基因的表达受雄激素的下调，该基因可能与雄激素剥夺后诱导细胞凋亡有关。由于Liprinα-2基因在雄激素非依赖性前列腺癌细胞系(PC-3、DU-145)或激素非依赖性前列腺癌组织中的表达完全消失，提示该基因在激素非依赖性前列腺癌细胞的诱导中起重要作用。

项目成果

Fujinami K, Uemura H, Ishiguro H, Kubota Y: "Liprin? 2 gene, protein tyrosine phosphate LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP"Int. J. of Mol Med. 10. 173-176 (2002)

Fujinami K、Uemura H、Ishiguro H、Kubota Y：“Liprin?2 基因、蛋白酪氨酸磷酸 LAR 相互作用蛋白相关基因，在人前列腺癌细胞系 LNCaP 中被雄激素下调”Int。

Miyoshi Y et al.: "Fluorescence in situ hybridization evaluation of c-myc and androgen receptor gene amplification and chromosomal anomalies in prostate cancer in Japanese patients"The Prostate. 43. 225-232 (2001)

Miyoshi Y等人：“日本患者前列腺癌中c-myc和雄激素受体基因扩增和染色体异常的荧光原位杂交评估”前列腺。

Ishiguro H et al.: "55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with androgen receptor"Int. J. Cancer. 105(1). 26-32 (2003)

Ishiguro H 等人：“55 kDa 核基质蛋白 (nmt55) mRNA 在人前列腺癌组织中表达，并与雄激素受体相关”Int.

Fujinami K et al.: "Liprin-α2 gene, protein tyrosine phosphate LAR interacting prostein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP"Int. J. of Mol Med. 10. 173-176 (2002)

Fujinami K 等人：“Liprin-α2 基因，与蛋白酪氨酸磷酸 LAR 相互作用的前列腺蛋白相关基因，在人前列腺癌细胞系 LNCaP 中被雄激素下调”，《Mol Med》杂志 10. 173-176 (2002)。

Ishiguro H, Uemura H, Fujinami K, Ikeda N, Ohta S, Kubota Y: "55 kDa nuclear matrix protein (nmt55) mRNA is expressed in human prostate cancer tissue and is associated with androgen receptor"Int. J. Cancer. 105(1). 26-32 (2003)

Ishiguro H、Uemura H、Fujinami K、Ikeda N、Ohta S、Kubota Y：“55 kDa 核基质蛋白 (nmt55) mRNA 在人前列腺癌组织中表达，并与雄激素受体相关”Int。