权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Role of NF-κB activation in hormone-refractory prostate cancer

NF-κB 激活在激素难治性前列腺癌中的作用

基本信息

批准号：
15591685
负责人：
NISHIMURA Kazuo
金额：
$ 2.24万
依托单位：
Osaka 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-15591685/
关键词：
NF-κB RANKL IL-6 IL-8 VEGF NF-κB 前立腺癌グルココルチコイドレセプター

项目摘要

Establishment of xenograft models using prostate cancer cell lines and osteblastic cell linesXenograft models using LNCaP, MDA-PCa2b and LNCaP mixed with MC3T3-E1cells were established on dorsal subcutaneous lesion of nude mice.Assessment of the expression of NF-κB, androgen receptor, and SRC-3 by immunohistochemical studyXenograft samples and clinical prostate samples obtained from patients with hormone-naive or hormone-refractory prostate cancer were used for immunohistochemical analysis. NF-κB mainly showed cytoplasmic expression in both xenografts and any stage of clinical prostate cancer. Less than 20% of cancer cells showed nuclear NF-κB expression in these samples. Higher gleason grade tumors had higher percentage of positivity of nuclear NF-κB expression.Expression levels of androgen receptor and SRC-3 in clinical prostate cancer were correlated.The effect of prostate cancer on oeteoclastgenesisCrude conditioned medium (CM) from LNCaP, DU145, PC3 and MDA PCa2b cells enhanced mRNA for receptor activator of NF-κB ligand (RANKL) in MC3T3-E1cells. However, these CM did not affect osteoprotegerin (OPG) mRNA expression in MC3T3-E1cells. CM from LNCaP, DU145 cells also enhanced maturation of osteoclast precursor cells (Cancer letter, in press).Serum levels of IL-6, TGF-β1, IL8 and VEGF in patients with hormone-refractory prostate cancerAfter disease progression, serum IL-6 levels significantly elevated, whereas serum TGF-β1 levels significantly declined. Higher serum IL-6 levels had significant association with poor prognosis, whereas higher serum TGF-β1 levels did not. After disease progression, serum IL-8 and VEGF levels increased marginally.The effect of NF-κB inhibitor, MG132, on prostate cancer growthA proteosomal inhibitor, MG132, inhibits the activation of NF-κB. MG132 inhibited the growth of LNCaP, DU145 and PC3 cells significantly in vitro.

前列腺癌细胞系和成骨细胞系异种移植模型的建立采用LNCaP、MDA-PCa 2 B和LNCaP与MC 3 T3-E1细胞混合移植于裸鼠背部皮下，检测NF-κB、雄激素受体、和SRC-3的免疫组化研究异种移植物样品和临床前列腺样品获得的患者的前列腺初治或激素，难治性前列腺癌用于免疫组织化学分析。NF-κB在移植瘤和临床分期的前列腺癌中均以胞浆表达为主。在这些样本中，不到20%的癌细胞显示核NF-κB表达。前列腺癌对破骨细胞生成的影响LNCaP、DU 145、PC 3和MDA PCa 2b细胞的粗条件培养液（CM）可增强MC 3 T3-E1细胞中NF-κB受体激活因子配体（RANKL）的mRNA表达。然而，这些CM不影响MC 3 T3-E1细胞中骨保护素（OPG）mRNA的表达。来自LNCaP、DU 145细胞的CM也促进破骨细胞前体细胞的成熟（Cancer Letter，in press）。血清IL-6水平升高与预后不良相关，而血清TGF-β1水平升高与预后不良无关。NF-κB抑制剂MG 132对前列腺癌生长的影响蛋白体抑制剂MG 132可抑制NF-κB的活化。MG 132对LNCaP、DU 145和PC 3细胞的生长有明显的抑制作用。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Expression of SRC-3(steroid receptor co-activator-3) in prostate cancer

SRC-3(类固醇受体辅激活剂-3)在前列腺癌中的表达

DOI：
发表时间：
2004
期刊：
Proceeding of the 15^<th> workshop on prostate cancer
影响因子：
0
作者：
Kawakami T;Okamoto K et al.;Shimizu Kiyonori
通讯作者：
Shimizu Kiyonori

Expression of SRC-3 (steroid receptor co-activator-3) in prostate cancer

SRC-3（类固醇受体辅激活剂-3）在前列腺癌中的表达

DOI：
发表时间：
2004
期刊：
Proceeding of the 15^<th> workshop on prostate cancer
影响因子：
0
作者：
Rao CN;Segawa T;Navari JR;Xu L;Srivastava S;Moul JW;Phillips B.;Matsuoka Yasuhiro et al.;Shimizu Kiyonori
通讯作者：
Shimizu Kiyonori

The treatment for hormone-refractory prostate cancer.

激素难治性前列腺癌的治疗。

DOI：
发表时间：
2003
期刊：
Educational courses of Japanese urological association 8
影响因子：
0
作者：
Inoue K;Chikazawa M;Fukata S;Yoshikawa C;Shuin T.;Nishimura K et al.;Nishimura Kazuo;Nishimura K
通讯作者：
Nishimura K

Modulation of androgen receptor transactivation by gelsolin: a newly identified androgen receptor coregulator.

DOI：
发表时间：
2003-08
期刊：
Cancer research
影响因子：
11.2
作者：
K. Nishimura;H. Ting;Y. Harada;T. Tokizane;N. Nonomura;Hong-Yo Kang;Hong-Chiang Chang;S. Yeh;H. Miyamoto;M. Shin;K. Aozasa;A. Okuyama;Chawnshang Chang
通讯作者：
K. Nishimura;H. Ting;Y. Harada;T. Tokizane;N. Nonomura;Hong-Yo Kang;Hong-Chiang Chang;S. Yeh;H. Miyamoto;M. Shin;K. Aozasa;A. Okuyama;Chawnshang Chang

前立腺癌におけるSRC-3の発現に関する免疫組織学的検討

前列腺癌中SRC-3表达的免疫组织化学研究