title: Flotillin-1 expression in human clear-cell renal cell carcinoma is associated with cancer progression and poor patient survival.
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 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.
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Yiyan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Jijun
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Fengkun
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Pei
authors.affiliation: Department of Nephrology, First Affiliated Hospital of Chinese PLA General Hospital, Beijing 100048, P.R. China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Yao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D007680:Kidney Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D009366:Neoplasm Seeding; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D014183:Transplantation, Heterologous
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C106354:flotillins