The H6D variant of NAG-1/GDF15 inhibits prostate xenograft growth in vivo.
The H6D variant of NAG-1/GDF15 inhibits prostate xenograft growth in vivo.
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DOI：
10.1002/pros.21471
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发表时间：
2012-05-01
期刊：
影响因子：
2.8
通讯作者：
Eling, Thomas E.
中科院分区：
文献类型：
--
作者：
Wang, Xingya;Chrysovergis, Kali;Bienstock, Rachelle J.;Shim, Minsub;Eling, Thomas E.
非甾体抗炎药激活基因（NAG-1）是转化生长因子β超家族的一个分支，参与炎症、早期骨形成、细胞凋亡和肿瘤发生等多种细胞过程。最近的临床研究表明，在NAG-1蛋白的位置6（组氨酸到天冬氨酸取代，或H6 D）的C到G单核苷酸多态性与较低的人类前列腺癌发病率相关。本研究的目的是研究NAG-1 H6 D变体在体内前列腺癌肿瘤发生中的活性。将表达H6 D NAG-1或野生型NAG-1的人前列腺癌DU 145细胞皮下注射到裸鼠中，并监测肿瘤生长。收集血清和肿瘤样品用于后续分析。H6 D变体比野生型NAG-1更有效，并且与对照小鼠相比显著抑制肿瘤生长。具有表达野生型NAG-1的肿瘤的小鼠比具有H6 D变体肿瘤的小鼠具有更大的体重和腹部脂肪减少，表明野生型NAG-1和H6 D NAG-1的不同活性。在荷瘤小鼠中观察到脂联素、瘦素和IGF-1血清水平的显著降低，在H6 D变体表达的情况下观察到更显著的降低。在肿瘤中细胞周期蛋白D1的表达被抑制，在表达H6 D变体的肿瘤中观察到显著减少。我们的数据表明，NAG-1的H6 D变体通过抑制IGF-1和Cyclin D1表达来抑制前列腺肿瘤发生，但可能还有其他机制。
Nonsteroidal anti-inflammatory drug-activated gene (NAG-1), a divergent member of the transforming growth factor beta superfamily, has been implicated in many cellular processes, including inflammation, early bone formation, apoptosis, and tumorigenesis. Recent clinical studies suggests that a C to G single nucleotide polymorphism at position 6 (histidine to aspartic acid substitution, or H6D) of the NAG-1 protein is associated with lower human prostate cancer incidence. The objective of the current study is to investigate the activity of NAG-1 H6D variant in prostate cancer tumorigenesis in vivo. Human prostate cancer DU145 cells expressing the H6D NAG-1 or wild-type NAG-1 were injected subcutaneously into nude mice and tumor growth was monitored. Serum and tumor samples were collected for subsequent analysis. The H6D variant was more potent than the wild-type NAG-1 and inhibited tumor growth significantly compared to control mice. Mice with tumors expressing the wild-type NAG-1 have greater reduced both body weight and abdominal fat than mice with H6D variant tumors suggesting different activities of the wild-type NAG-1 and the H6D NAG-1. A significant reduction in adiponectin, leptin and IGF-1 serum levels was observed in the tumor bearing mice with a more profound reduction observed with expression of H6D variant. Cyclin D1 expression was suppressed in the tumors with a dramatic reduction observed in the tumor expressing the H6D variant. Our data suggest that the H6D variant of NAG-1 inhibits prostate tumorigenesis by suppressing IGF-1 and Cyclin D1 expression but likely additional mechanisms are operative.
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影响因子：
5.6
作者：
Huang, Chih-Yang;Yu, Hsin-Shan;Tang, Chih-Hsin
通讯作者：
Tang, Chih-Hsin
影响因子：
11.4
作者：
Kotzsch, Alexander;Nickel, Joachim;Mueller, Thomas D.
通讯作者：
Mueller, Thomas D.
影响因子：
29.4
作者：
Baek, Seung Joon;Okazaki, Ryuji;Eling, Thomas E.
通讯作者：
Eling, Thomas E.
影响因子：
2.9
作者：
Allendorph, George P.;Isaacs, Michael J.;Choe, Senyon
通讯作者：
Choe, Senyon
DOI：
10.1590/s0004-27302009000800010
发表时间：
2009-11-01
期刊：
Arquivos Brasileiros de Endocrinologia & Metabologia
影响因子：
--
作者：
Lima, Giovanna A. Balarini;Corrêa, Lívia L.;Gadelha, Mônica R.
通讯作者：
Gadelha, Mônica R.