Ratcliffe Peter J
The Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington Campus, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
Cancer Cell. 2007 Apr;11(4):303-5. doi: 10.1016/j.ccr.2007.03.015.
Molecular genetic analysis of hereditary leiomyomatosis and renal cell cancer (HLRCC) unexpectedly revealed germline defects in the gene encoding the Krebs cycle enzyme fumarate hydratase (FH), stimulating great interest in the underlying mechanism of oncogenesis. It has been proposed that the associated accumulation of fumarate competitively inhibits the 2-oxoglutarate-dependent dioxygenases that regulate hypoxia-inducible factor (HIF), thus activating oncogenic hypoxia pathways. In this issue of Cancer Cell, Pollard and colleagues describe a genetic mouse model of FH deficiency that recapitulates aspects of the human disease, including HIF activation and renal cysts, enabling further insights into this unusual cancer syndrome.
遗传性平滑肌瘤病和肾细胞癌（HLRCC）的分子遗传学分析意外地揭示了编码三羧酸循环酶延胡索酸水合酶（FH）的基因中的种系缺陷，这引发了人们对肿瘤发生潜在机制的极大兴趣。有人提出，相关的富马酸积累竞争性抑制调节缺氧诱导因子（HIF）的2-氧戊二酸依赖性双加氧酶，从而激活致癌性缺氧途径。在本期《癌细胞》杂志中，波拉德及其同事描述了一种FH缺陷的基因小鼠模型，该模型概括了人类疾病的一些方面，包括HIF激活和肾囊肿，从而能够进一步深入了解这种不寻常的癌症综合征。
