Flotillin-1 expression in human clear-cell renal cell carcinoma is associated with cancer progression and poor patient survival.
Flotillin-1 expression in human clear-cell renal cell carcinoma is associated with cancer progression and poor patient survival.
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DOI：
10.3892/mmr.2014.2310
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发表时间：
2014-08
影响因子：
3.4
通讯作者：
Yiyan Zhang;Ji-jun Li;Yan Song;Feng-kun Chen;Y. Pei;Fenghua Yao
中科院分区：
文献类型：
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作者：
Yiyan Zhang;Ji-jun Li;Yan Song;Feng-kun Chen;Y. Pei;Fenghua Yao
本研究旨在探讨FLOT1基因编码的整合膜蛋白FLOTLIN-1在人肾透明细胞癌(RCC)中的表达水平及其增殖作用。Flotillin还与其他类型的癌症有关，但Flotillin在肾癌中的作用尚未确定。应用免疫组织化学和Western blotting方法检测182例肾切除患者肾细胞癌组织中FLOT1蛋白的表达水平。逆转录(RT)和RT-定量聚合酶链式反应(PCR)分析FLOT1基因的表达水平。用Kaplan-Meier分析检验肿瘤标本中FLOT1表达水平与患者生存时间之间的关系。为证实FLOT1对肾癌细胞的增殖作用，将FLOT1载体导入4种肾癌细胞系，并用小干扰RNA抑制FLOT1的表达。采用WST-1比色法和BALB/C裸鼠移植瘤实验研究肾癌细胞的增殖能力。结果表明，FLOT1在肾癌组织中的表达水平显著高于正常肾组织，且与肿瘤的分期、大小和组织学分级有关。此外，FLOT1在体外和体内均能显著促进肾癌细胞系的增殖。这些发现表明，在肾癌中上调的FLOT1参与了肾癌细胞的增殖、肿瘤的发生和发展。因此，FLOT1是透明细胞肾癌患者独立的预后标志物和治疗靶点。
The present study was designed to elucidate the expression levels and the proliferative effect of flotillin-1, an integral membrane protein encoded by the FLOT1 gene, in human clear-cell renal cell carcinoma (RCC). Flotillin has been implicated in other types of cancer, but the role of flotillin in RCC has not been established. Immunohistochemistry and western blotting were used to determine FLOT1 protein expression levels in RCC samples from 182 patients who underwent nephrectomy. FLOT1 mRNA expression levels were analyzed using reverse-transcription (RT) and RT-quantitative polymerase chain reaction (PCR). The association between FLOT1 expression levels in the tumor samples and patient survival time was examined using Kaplan‑Meier analysis. To demonstrate the proliferative effect of FLOT1 on RCC cells, a FLOT1 vector was transfected into four RCC cell lines and FLOT1 expression was inhibited using small interfering RNA. The proliferative ability of the RCC cells was investigated using a WST-1 assay and xenograft experiments with BALB/C nude mice. The results demonstrated that FLOT1 expression levels were significantly higher in RCC cell samples from patients than in healthy renal tissue, and the expression levels were associated with tumor stage, size and histological grade. In addition, FLOT1 significantly enhanced the proliferation of RCC cell lines in vitro and in vivo. These findings suggest that FLOT1, which is upregulated in RCC, is involved in RCC cell proliferation, tumorigenesis and progression. Therefore, FLOT1 is an independent prognostic marker and therapeutic target for patients with clear-cell RCC.