Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma.

Citation:
Morris MR, Maina E, Morgan NV, Gentle D, Astuti D, Moch H, Kishida T, Yao M, Schraml P, Richards FM, Latif F, Maher ER. "Molecular genetic analysis of FIH-1, FH, and SDHB candidate tumour suppressor genes in renal cell carcinoma." J. Clin. Pathol.. 2004;57(7):706-11.

Abstract:

Overexpression of the hypoxia inducible factor 1 (HIF-1) and HIF-2 transcription factors and the consequent upregulation of hypoxia inducible mRNAs is a feature of many human cancers and may be unrelated to tissue hypoxia. Thus, the VHL (von Hippel-Lindau) tumour suppressor gene (TSG) regulates HIF-1 and HIF-2 expression in normoxia by targeting the alpha subunits for ubiquitination and proteolysis. Inactivation of the VHL TSG in VHL tumours and in sporadic clear cell renal cell carcinoma (RCC) results in overexpression of HIF-1 and HIF-2. However, RCC without VHL inactivation may demonstrate HIF upregulation, suggesting that VHL independent pathways for HIF activation also exist. In RCC, three candidate HIF activating genes exist-FIH-1 (factor inhibiting HIF), SDHB, and FH-which may be dependent or independent of VHL inactivation.

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