Cancer Cell. 2011 Oct 18;20(4):511-23. doi: 10.1016/j.ccr.2011.08.024.

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

Ooi A, Wong JC, Petillo D, Roossien D, Perrier-Trudova V, Whitten D, Min BW, Tan MH, Zhang Z, Yang XJ, Zhou M, Gardie B, Molinié V, Richard S, Tan PH, Teh BT, Furge KA.

Source

Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, MI 49503, USA.

Abstract

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.

Comment in

Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2. [Cancer Cell. 2011]
Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2.Kinch L, Grishin NV, Brugarolas J. Cancer Cell. 2011 Oct 18; 20(4):418-20.
Kidney tumours. 'NRF said. [Nat Rev Cancer. 2011]
Kidney tumours. 'NRF said.McCarthy N. Nat Rev Cancer. 2011 Nov 10; 11(12):833. Epub 2011 Nov 10.

PMID:: 22014576; [PubMed - indexed for MEDLINE]

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Cited by 12 PubMed Central articles

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The Keap1-Nrf2 system in cancers: stress response and anabolic metabolism.
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Cancer Cell. 2011 Oct 18 ;20(4):511-23. doi: 10.1016/j.ccr.2011.08.024.

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