Functional and Expression Analyses of Endoplasmic Reticulum Stress Response Genes in Prostate Cancer

前列腺癌内质网应激反应基因的功能和表达分析

• 批准号: 15591684
• 负责人: SEGAWA Takehiko
• 金额: $ 2.3万
• 依托单位: Kyoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591684/
• 关键词: Prostate Cancer; Androgen; Endoplasmic Reticulum Stress; NDRG1; Tissue Microarray

NDRG1, which was originally identified as a N-myc downstream-regulated gene, is now considered to play a role in cell growth, differentiation, carcinogenesis as well as cellular stress responses. We have reported that the expressions of ER stress responsive genes including NDRG1 were regulated by androgen in a time and dose dependent manner in LNCaP, and that the RNA expression of NDRG1 was decreased in prostate cancer (CaP) compared to normal prostate. In this study we investigated the effects of NDRG1 on the androgen sensitivity in LNCaP cells. LNCaP clones stably expressing NDRG1 (LNCaP-NDRG1) were obtained. Parental LNCaP and LNCaP-NDRG1 cells were cultured without androgen, and then stimulated with synthetic androgen R1881 at 0.01 nM to 100 nM concentrations. Cell proliferation was examined by MTT assay. Proliferation of LNCaP was bi-phasically regulated by androgen, with the optimum of 0.1nM R1881 stimulation, as reported. The optimal condition for LNCaP-NDRG1 cells was shifted t … More o higher R1881 concentration than parental LNCaP cells, suggesting an effect of NDRG1 on the androgen sensitivity in LNCaP cells. Then, we analyzed the protein expressions of NDRG1 and androgen receptor (AR) in radical prostatectomy specimens to investigate the impact of NDRG1 expression on clinical or pathological features of CaP patients. Tissue microarray of 260 spots from 70 CaP patients was immunohistochemically analyzed. Expressions of NDRG1 and AR in CaP tissues were compared with those in normal tissues and correlation among NDRG1, AR expressions and clinical or pathological parameters were analyzed. NDRG1 was expressed both in normal and CaP epithelial cells, but not in stromal cells. When compared with normal tissues, NDRG1 protein expression was decreased in 47% of CaP tissues, consistent with RNA expression data. AR expression was positively correlated with NDRG1 expression, suggesting androgen-regulated expression of NDRG1 in CaP tissues. NDRG1 expression was not correlated with other clinical or pathological features, including Gleason score, and PSA failure after radical prostatectomy. Less

NDRG 1最初被鉴定为N-myc下游调控基因，现在被认为在细胞生长、分化、致癌以及细胞应激反应中起作用。我们已经报道了包括NDRG 1在内的ER应激反应基因的表达在LNCaP中受到雄激素的时间和剂量依赖性调节，并且NDRG 1的RNA表达在前列腺癌（CaP）中比正常前列腺低。在这项研究中，我们研究了NDRG 1对LNCaP细胞雄激素敏感性的影响。获得稳定表达NDRG 1的LNCaP克隆（LNCaP-NDRG 1）。亲本LNCaP和LNCaP-NDRG 1细胞在没有雄激素的情况下培养，然后用0.01 nM至100 nM浓度的合成雄激素R1881刺激。MTT法检测细胞增殖;据报道，LNCaP的增殖受雄激素的双相调节，最佳刺激为0.1nM R1881。LNCaP-NDRG 1细胞的最适培养条件改变为： ...更多信息 〇比亲本LNCaP细胞更高的R1881浓度，表明NDRG 1对LNCaP细胞中的雄激素敏感性的影响。然后，我们分析了NDRG 1和雄激素受体（AR）在根治性前列腺切除术标本中的蛋白表达，以探讨NDRG 1表达对CaP患者临床或病理特征的影响。对70例CaP患者的260个组织芯片进行了免疫组化分析。比较NDRG 1和AR在CaP组织和正常组织中的表达情况，分析NDRG 1和AR表达与临床病理参数的相关性。NDRG 1在正常和CaP上皮细胞中均有表达，但在间质细胞中不表达。与正常组织相比，NDRG 1蛋白表达在47%的CaP组织中降低，与RNA表达数据一致。AR表达与NDRG 1表达呈正相关，表明雄激素调节NDRG 1在CaP组织中的表达。NDRG 1表达与其他临床或病理特征无关，包括Gleason评分和根治性前列腺切除术后PSA失败。少

项目成果

Effective treatment of advanced solid tumors by the combination of arsenic trioxide and L-buthionine-sulfoximine

• DOI: 10.1038/sj.cdd.4401389
• 发表时间: 2004-07-01
• 期刊: CELL DEATH AND DIFFERENTIATION
• 影响因子: 12.4
• 作者: Maeda, H;Hori, S;Kakizuka, A
• 通讯作者: Kakizuka, A

Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population

日本人群中 V89L SRD5A2 多态性与前列腺癌发病的关系

• DOI: 10.1097/01.ju.0000056152.57018.31
• 发表时间: 2003-06-01
• 期刊: JOURNAL OF UROLOGY
• 影响因子: 6.6
• 作者: Li, ZH;Habuchi, T;Kato, T
• 通讯作者: Kato, T

Androgern receptor, Ki67, and p53 expression in radical prostatectomy specimens predict treatment failure in Japanese population.

根治性前列腺切除术标本中雄激素受体、Ki67 和 p53 的表达可预测日本人群的治疗失败。

• 发表时间: 2005
• 期刊: Urology (in press)
• 作者: Inoue T;Segawa T;Shiraishi T;Yoshida T;Toda Y;Yamada T;Kinukawa N;Kinoshita H;Kamoto T;Ogawa O.
• 通讯作者: Ogawa O.

Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia

• DOI: 10.1002/pros.10365
• 发表时间: 2004-06-01
• 期刊: PROSTATE
• 影响因子: 2.8
• 作者: Kakehi, Y;Segawa, T;Getzenberg, RH
• 通讯作者: Getzenberg, RH

Methylation of TFPI-2 gene is not the sole cause of its silencing.

TFPI-2基因的甲基化并不是其沉默的唯一原因。

• 发表时间: 2003
• 期刊: International Journal of Oncology 22
• 作者: Rao CN;Segawa T;Navari JR;Xu L;Srivastava S;Moul JW;Phillips B.
• 通讯作者: Phillips B.