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Free Radical Research Volume 45, 2011 - Issue 2
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Review Article

Stage-specific roles of fibulin-5 during oxidative stress-induced renal carcinogenesis in rats

Hiroki Ohara Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
,
Shinya Akatsuka Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan
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Hirotaka Nagai Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
,
Yu-Ting Liu Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
,
Li Jiang Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan
,
Yasumasa Okazaki Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan
,
Yoriko Yamashita Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, Japan
,
Tomoyuki Nakamura Department of Pharmacology, Kansai Medical University, Osaka 570-8506, Japan
&
Shinya Toyokuni Department of Pathology and Biological Responses, Graduate School of Medicine, Nagoya University, Showa-ku, Nagoya 466-8550, JapanCorrespondence[email protected]
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Pages 211-220 | Received 22 Aug 2010, Published online: 13 Oct 2010
 
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Abstract

By using a rat model of renal cell carcinoma (RCC) induced by ferric nitrilotriacetate (Fe-NTA), this study performed genome-wide analysis to identify target genes during carcinogenesis. It screened for genes with decreased expression in RCCs, with simultaneous loss of heterozygosity, eventually to focus on the fibulin-5 (fbln5) gene. Oxidative damage via Fe-NTA markedly increased Fbln5 in the proximal tubules. RCCs presented lower levels of Fbln5. However, a fraction of RCCs presenting pulmonary metastasis revealed significantly higher levels of Fbln5 than those without metastasis, accompanied by immunopositivity of RCC cells and myofibroblast proliferation. Experiments revealed that RCC cell lines showed lower expression of fbln5 than its non-transformed counterpart NRK52E, but that fbln5 transfection to RCC cell lines changed neither proliferation nor migration/invasion. The data suggest that Fbln5 plays a role not only in the tissue repair and remodelling after renal tubular oxidative damage but also in RCC metastasis, presumably as a cytokine.

This paper was first published online on Early Online on 4 October 2010.

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