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Accession IconGSE26574

An antioxidant response phenotype is shared between hereditary and sporadic type 2 papillary renal cell carcinoma

Organism Icon Homo sapiens
Sample Icon 64 Downloadable Samples
Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

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Description
Fumarate hydratase (FH) mutation causes hereditary type 2 papillary renal cell carcinoma (HLRCC, Hereditary Leiomyomatosis and Renal Cell Cancer (MM ID # 605839)). The main effect of FH mutation is fumarate accumulation. The current paradigm posits that the main consequence of fumarate accumulation is HIF-a stabilization. Paradoxically, FH mutation differs from other HIF-a 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 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.
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