Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis
Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis
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DOI：
10.1002/pros.20681
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发表时间：
2008-02-15
期刊：
影响因子：
2.8
通讯作者：
Habuchi, Tomonori
中科院分区：
文献类型：
--
作者：
Narita, Shintaro;Tsuchiya, Norihiko;Habuchi, Tomonori
背景。多项研究表明，高脂肪饮食 (HFD) 可能是前列腺癌 (PCa) 的危险因素。作为描绘 HFD 下 PCa 进展加速的分子机制的第一步，我们研究了 HFD 和低脂饮食 (LFD) 下人类 PCa 异种移植物的差异基因表达。方法。将LNCaP细胞皮下注射到20只裸鼠体内，将其平均分为两组：HFD组和LFD组。使用HFD和LFD的小鼠异种移植物进行寡核苷酸微阵列分析，并通过定量RT-PCR实验验证具有显着差异表达的候选基因的结果。对于胰岛素样生长因子I受体（IGF-IR），通过免疫组织化学进一步检测异种移植组织和78例根治性前列腺切除标本中的蛋白表达水平。 HFD 组的肿瘤体积和血清 PSA 水平显着高于 LFD 组（分别为 P < 0.001 和 P = 0.006）。我们发现 HFD 异种移植物中有 64 个上调基因 (0.19%) 和 14 个下调基因 (0.04%)，差异超过两倍。 IGF-IR、TNFRSF 和 LPL 在定量 RT-PCR 实验中显示出显着差异。免疫染色进一步显示 HFD 异种移植物中 IGF-IR 表达显着增强。在人类 PCa 中，IGF-IR 免疫反应性最低的组往往在正常和 PCa 上皮中具有最低的体重指数。结论。 HFD 诱导大量基因 mRNA 显着上调和下调。此外，IGF-I 系统可能参与 HFD 相关的 PCa 进展加速。
BACKGROUND. Several studies have suggested that a high fat diet (HFD) maybe a risk factor of prostate cancer (PCa). As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft under HFD and a low fat diet (LFD).METHODS. LNCaP cells were subcutaneously injected in 20 nude mice, which were equally divided into two groups, the HFD group and LFD group. Oligonucleotide microarray analyses were performed using mice xenografts from HFD and LFD, and the results of candidate genes with a significant differential expression were validated by quantitative RT-PCR experiments. As for insulin-like growth factor I receptor (IGF-IR), protein expression levels were further examined by immunohistochemistry in xenograft tissues and in 78 radical prostatectomy specimens.RESULTS. Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group (P < 0.001 and P = 0.006, respectively). We found 64 up-regulated genes (0.19%) and 14 down-regulated genes (0.04%) with more than twofold differences in the HFD xenograft. IGF-IR, TNFRSF, and LPL showed striking differences in the quantitative RT-PCR experiment. Immunostaining further revealed marked enhanced IGF-IR expression in the HFD xenograft. In human PCa, the lowest IGF-IR immuncreactivity group tended to have the lowest body mass index in both normal and PCa epithelium.CONCLUSION. HFD induced remarkable up- and down-regulation of mRNA of a substantial number of genes. Furthermore, the IGF-I system may be involved in the HFD-associated enhanced progression of PCa.