HIF-1alpha and HIF-2alpha have divergent roles in colon cancer.
HIF-1alpha and HIF-2alpha have divergent roles in colon cancer.
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HIF-1α 和 HIF-2α 在结肠癌中具有不同的作用。
DOI：
10.1002/ijc.24032
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发表时间：
2009-02-15
影响因子：
6.4
通讯作者：
Chung, Daniel C.
中科院分区：
文献类型：
--
作者：
Imamura, Takaaki;Kikuchi, Hirotoshi;Herraiz, Maria-Teresa;Park, Do-Youn;Mizukami, Yusuke;Mino-Kenduson, Mari;Lynch, Maureen P.;Rueda, Bo R.;Benita, Yair;Xavier, Ramnik J.;Chung, Daniel C.
缺氧诱导因子（HIF）-1和HIF-2是介导细胞缺氧反应的异二聚体转录因子。它们的关键调节亚基HIF-1α和HIF-2α在缺氧条件下的诱导作用相似，但它们在癌症中的功能作用可能是不同的和亚型特异性的。建立了稳定表达HIF-1α、HIF-2α或两者的siRNA的SW 480结肠癌细胞株。在软琼脂试验中，HIF-1α缺陷的细胞显示较低的增殖和迁移率，但HIF-2α缺陷的细胞显示增强的锚定非依赖性生长。异种移植研究表明，HIF-1α缺乏抑制了整体肿瘤生长，而HIF-2α缺乏则刺激了肿瘤生长。在人结肠癌组织中，HIF-1α和HIF-2α（在较小程度上）的表达与VEGF和肿瘤血管生成的上调有关。然而，HIF-2α而非HIF-1α表达的缺失与晚期肿瘤密切相关。DNA微阵列分析确定了不同的HIF-1α和HIF-2α靶基因，可能解释这些表型差异。总的来说，这些发现表明HIF亚型在结肠癌中可能具有不同的细胞功能。HIF-1α促进SW 480结肠癌细胞的生长，而HIF-2α则抑制其生长。因此，靶向HIF的治疗方法可能需要考虑这些异构体特异性特性。
Hypoxia-inducible factor (HIF)-1 and HIF-2 are heterodimeric transcription factors that mediate the cellular response to hypoxia. Their key regulatory subunits, HIF-1α and HIF-2α, are induced similarly by hypoxia, but their functional roles in cancer may be distinct and isoform-specific. SW480 colon cancer cells with stable expression of siRNA to HIF-1α or HIF-2α or both were established. HIF-1α-deficient cells displayed lower rates of proliferation and migration, but HIF-2α-deficient cells exhibited enhanced anchorage independent growth in a soft agar assay. Xenograft studies revealed that HIF-1α deficiency inhibited overall tumor growth, whereas deficiency of HIF-2α stimulated tumor growth. In human colon cancer tissues, expression of HIF-1α and to a lesser extent, HIF-2α, was linked to upregulation of VEGF and tumor angiogenesis. However, loss of expression of HIF-2α but not HIF-1α was strongly correlated with advanced tumor stage. DNA microarray analysis identified distinct sets of HIF-1α and HIF-2α target genes that may explain these phenotypic differences. Collectively, these findings suggest that HIF isoforms may have differing cellular functions in colon cancer. In particular, HIF-1α promoted the growth of SW480 colon cancer cells but HIF-2α appeared to restrain growth. Consequently, therapeutic approaches that target HIF may need to consider these isoform-specific properties.
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影响因子：
20.1
作者：
Cazes, Aurelie;Galaup, Ariane;Monnot, Catherine
通讯作者：
Monnot, Catherine
DOI：
10.1073/pnas.0609025103
发表时间：
2006-12-05
影响因子：
11.1
作者：
Galaup, Ariane;Cazes, Aurelie;Germain, Stephane
通讯作者：
Germain, Stephane
影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
11.5
作者：
Creighton-Gutteridge, Mark;Cardellina, John H., II;Melillo, Giovanni
通讯作者：
Melillo, Giovanni
影响因子：
11.2
作者：
Dang, DT;Chen, F;Dang, LH
通讯作者：
Dang, LH