Abstract

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 182patients 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 invitro and invivo. 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.

Highlights

  • Human renal cell carcinoma (RCC) is the most common and lethal type of malignant kidney tumor

  • The present study found that FLOT1 expression was increased in patients with RCC compared with normal individuals

  • One study demonstrated that FLOT1 expression levels are associated with aggressive hepatocellular carcinoma and may be used as a prognostic marker in patients with this disease [33]

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Summary

Introduction

Human renal cell carcinoma (RCC) is the most common and lethal type of malignant kidney tumor. As lipid rafts have been reported to be involved in the initiation and development of numerous types of cancer [15,16], lipid rafts may be novel therapeutic targets against malignant tumors [17,18]. FLOT1 and FLOT2 activate signal transductions by binding with membrane-resident receptor kinases. In addition to FLOT1 and FLOT2 functions in cellular and organelle membranes, flotillins are involved in tumorigenesis and the progression of different types of human tumor [25,26]. The expression levels of FLOT1 and its effect on the proliferative ability of human RCC cells were investigated

Materials and methods
Results
Discussion
Athar U and Gentile TC
Coppin C
Simpson D and Curran MP
16. Patra SK and Bettuzzi S
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