An Antioxidant Response Phenotype Shared between Hereditary and Sporadic Type 2 Papillary Renal Cell Carcinoma

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• 作者：Aikseng Ooi¹ ; Jing-Chii Wong² ; David Petillo¹ ; Douglas Roossien¹ ; Victoria Perrier-Trudova¹ ;   ; ³ ; Douglas Whitten⁴ ; Bernice  ; Wong  ; Hui Min² ; Min-Han Tan² ; Zhongfa Zhang¹ ;   ; ⁹ ; Ximing  ; J. Yang⁵ ; Ming Zhou⁶ ; Betty Gardie³ ; Vincent Molinié ; ³ ; Sté ; phane Richard³ ; Puay  ; Hoon Tan⁷ ; Bin  ; Tean Teh¹ ;   ; ² ;   ; ^{bin.teh@vai.org} ; Kyle  ; A. Furge⁸ ;   ; ^{kyle.furge@vai.org}
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：18 October 2011
• 年：2011
• 卷：20
• 期：4
• 页码：511-523
• 全文大小：2525 K

文摘

Summary

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-¦Á stabilization. Paradoxically, FH mutation differs from other HIF-¦Á 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)¨Ccontrolled 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.