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

Research output: Contribution to journalArticle

238 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

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    Ooi, A., Wong, J. C., Petillo, D., Roossien, D., Perrier-Trudova, V., Whitten, D., Min, B. W. H., Tan, M. H., Zhang, Z., Yang, X. J., Zhou, M., Gardie, B., Molinié, V., Richard, S., Tan, P. H., Teh, B. T., & Furge, K. A. (2011). An Antioxidant Response Phenotype Shared between Hereditary and Sporadic Type 2 Papillary Renal Cell Carcinoma. Cancer Cell, 20(4), 511-523. https://doi.org/10.1016/j.ccr.2011.08.024