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CYP1B1 promotes tumorigenesis via altered expression of CDC20 and DAPK1 genes in renal cell carcinoma

Authors
 Yozo Mitsui  ;  Inik Chang  ;  Shinichiro Fukuhara  ;  Miho Hiraki  ;  Naoko Arichi  ;  Hiroaki Yasumoto  ;  Hiroshi Hirata  ;  Soichiro Yamamura  ;  Varahram Shahryari  ;  Guoren Deng  ;  Darryn K. Wong  ;  Shahana Majid  ;  Hiroaki Shiina  ;  Rajvir Dahiya  ;  Yuichiro Tanaka 
Citation
 BMC Cancer, Vol.15 : 942, 2015 
Journal Title
 BMC Cancer 
Issue Date
2015
MeSH
Apoptosis ; Carcinoma, Renal Cell/genetics* ; Carcinoma, Renal Cell/metabolism ; Carcinoma, Renal Cell/pathology ; Cdc20 Proteins/genetics* ; Cdc20 Proteins/metabolism ; Cell Line, Tumor ; Cell Movement ; Cytochrome P-450 ; CYP1B1/genetics* ; Cytochrome P-450 CYP1B1/metabolism ; Death-Associated Protein Kinases/genetics* ; Death-Associated Protein Kinases/metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Kidney Neoplasms/genetics* ; Kidney Neoplasms/metabolism ; Kidney Neoplasms/pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Up-Regulation
Abstract
BACKGROUND: Cytochrome P450 1B1 (CYP1B1) has been shown to be up-regulated in many types of cancer including renal cell carcinoma (RCC). Several reports have shown that CYP1B1 can influence the regulation of tumor development; however, its role in RCC has not been well investigated. The aim of the present study was to determine the functional effects of CYP1B1 gene on tumorigenesis in RCC. METHODS: Expression of CYP1B1 was determined in RCC cell lines, and tissue microarrays of 96 RCC and 25 normal tissues. To determine the biological significance of CYP1B1 in RCC progression, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses. RESULTS: First, we confirmed that CYP1B1 protein expression was significantly higher in RCC cell lines compared to normal kidney tissue. This trend was also observed in RCC samples (p < 0.01). Interestingly, CYP1B1 expression was associated with tumor grade and stage. Next, we silenced the gene in Caki-1 and 769-P cells by RNA interference and performed various functional analyses to determine the biological significance of CYP1B1 in RCC progression. Inhibition of CYP1B1 expression resulted in decreased cell proliferation, migration and invasion of RCC cells. In addition, reduction of CYP1B1 induced cellular apoptosis in Caki-1. We also found that these anti-tumor effects on RCC cells caused by CYP1B1 depletion may be due to alteration of CDC20 and DAPK1 expression based on gene microarray and confirmed by real-time PCR. Interestingly, CYP1B1 expression was associated with CDC20 and DAPK1 expression in clinical samples. CONCLUSIONS: CYP1B1 may promote RCC development by inducing CDC20 expression and inhibiting apoptosis through the down-regulation of DAPK1. Our results demonstrate that CYP1B1 can be a potential tumor biomarker and a target for anticancer therapy in RCC.
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DOI
10.1186/s12885-015-1951-0
Appears in Collections:
2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
장인익(Chang, In Ik)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/157010
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