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

Aikseng Ooi, Jing Chii Wong, David Petillo, Douglas Roossien, Victoria Perrier-Trudova, Douglas Whitten, Bernice Wong Hui Min, Min Han Tan, Zhongfa Zhang, Ximing J. Yang, Ming Zhou, Betty Gardie, Vincent Molinié, Stéphane Richard, Puay Hoon Tan, Bin Tean Teh*, Kyle A. Furge

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

249 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)511-523
Number of pages13
JournalCancer Cell
Volume20
Issue number4
DOIs
StatePublished - Oct 18 2011

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'An Antioxidant Response Phenotype Shared between Hereditary and Sporadic Type 2 Papillary Renal Cell Carcinoma'. Together they form a unique fingerprint.

Cite this