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

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.

• Authors: Hiroki Ohara, Shinya Akatsuka, Hirotaka Nagai, Yu-Ting Liu, Li Jiang, Yasumasa Okazaki, Yoriko Yamashita, Tomoyuki Nakamura, Shinya Toyokuni
• Journal: Free radical research (Free Radic Res) Vol. 45 Issue 2 Pg. 211-20 (Feb 2011) ISSN: 1029-2470 [Electronic] England
• PMID: 20942562 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Extracellular Matrix Proteins
• Fbln5 protein, rat
• Ferric Compounds
• Recombinant Proteins
• Nitrilotriacetic Acid
• ferric nitrilotriacetate

Topics

• Animals
• Base Sequence
• Carcinoma, Renal Cell (chemically induced, genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Transformation, Neoplastic (metabolism, pathology)
• Disease Models, Animal
• Extracellular Matrix Proteins (genetics, metabolism)
• Ferric Compounds (administration & dosage, adverse effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Genome-Wide Association Study
• Immunohistochemistry
• Kidney Neoplasms (chemically induced, genetics, metabolism, pathology)
• Kidney Tubules, Proximal (drug effects, metabolism, pathology)
• Loss of Heterozygosity (genetics)
• Lung Neoplasms (secondary)
• Male
• Microsatellite Repeats
• Molecular Sequence Data
• Nitrilotriacetic Acid (administration & dosage, adverse effects, analogs & derivatives)
• Oligonucleotide Array Sequence Analysis
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Rats
• Rats, Wistar
• Recombinant Proteins (genetics, metabolism)
• Signal Transduction (drug effects)