An Antioxidant Response Phenotype Shared between Hereditary and Sporadic Type 2 Papillary Renal Cell Carcinoma
Copyright policy )An Antioxidant Response Phenotype Shared between Hereditary and Sporadic Type 2 Papillary Renal Cell Carcinoma
Fumarate hydratase (FH) mutation causes hereditary type 2 papillary renal cell carcinoma (PRCC2). The main effect of FH mutation is fumarate accumulation. The current paradigm posits that the main consequence of fumarate accumulation is HIF-α stabilization. Paradoxically, FH mutation differs from other HIF-α stabilizing mutations, such as VHL and SDH mutations, in its associated tumor types. We identified that fumarate can directly up-regulate antioxidant response element (ARE)-controlled genes. We demonstrated that aldo-keto reductase family 1 member B10 (AKR1B10) is an ARE-controlled gene and is up-regulated upon FH knockdown as well as in FH null cell lines. AKR1B10 overexpression is also a prominent feature in both hereditary and sporadic PRCC2. This phenotype better explains the similarities between hereditary and sporadic PRCC2.
- Michigan State University United States
- Van Andel Institute United States
- The Wistar Institute United States
- Cleveland Clinic United States
- The Wistar Institute
Cancer Research, Kelch-Like ECH-Associated Protein 1, NF-E2-Related Factor 2, Nuclear Respiratory Factor 1, Aldo-Keto Reductases, Intracellular Signaling Peptides and Proteins, Cell Biology, Hypoxia-Inducible Factor 1, alpha Subunit, Response Elements, Antioxidants, Kidney Neoplasms, Fumarate Hydratase, Gene Expression Regulation, Neoplastic, Phenotype, Oncology, Aldehyde Reductase, Cell Line, Tumor, Humans, RNA, Messenger, Carcinoma, Renal Cell
Cancer Research, Kelch-Like ECH-Associated Protein 1, NF-E2-Related Factor 2, Nuclear Respiratory Factor 1, Aldo-Keto Reductases, Intracellular Signaling Peptides and Proteins, Cell Biology, Hypoxia-Inducible Factor 1, alpha Subunit, Response Elements, Antioxidants, Kidney Neoplasms, Fumarate Hydratase, Gene Expression Regulation, Neoplastic, Phenotype, Oncology, Aldehyde Reductase, Cell Line, Tumor, Humans, RNA, Messenger, Carcinoma, Renal Cell
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