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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Base Sequence
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Carcinoma, Renal Cell / chemically induced
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Carcinoma, Renal Cell / genetics
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Carcinoma, Renal Cell / metabolism*
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Carcinoma, Renal Cell / pathology*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Cell Transformation, Neoplastic / metabolism
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Cell Transformation, Neoplastic / pathology
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Disease Models, Animal
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Extracellular Matrix Proteins* / genetics
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Extracellular Matrix Proteins* / metabolism
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Ferric Compounds / administration & dosage
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Ferric Compounds / adverse effects
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Gene Expression Regulation, Neoplastic / drug effects
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Genome-Wide Association Study
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Immunohistochemistry
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Kidney Neoplasms / chemically induced
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Kidney Neoplasms / genetics
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Kidney Neoplasms / metabolism*
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Kidney Neoplasms / pathology*
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Kidney Tubules, Proximal / drug effects
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Kidney Tubules, Proximal / metabolism
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Kidney Tubules, Proximal / pathology*
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Loss of Heterozygosity / genetics
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Lung Neoplasms / secondary*
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Male
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Microsatellite Repeats
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Molecular Sequence Data
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Nitrilotriacetic Acid / administration & dosage
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Nitrilotriacetic Acid / adverse effects
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Nitrilotriacetic Acid / analogs & derivatives
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Oligonucleotide Array Sequence Analysis
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Oxidation-Reduction
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Oxidative Stress / drug effects
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Rats
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Rats, Wistar
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Recombinant Proteins* / genetics
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Recombinant Proteins* / metabolism
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Signal Transduction / drug effects
Substances
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Extracellular Matrix Proteins
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Fbln5 protein, rat
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Ferric Compounds
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Recombinant Proteins
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Nitrilotriacetic Acid
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ferric nitrilotriacetate