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Cell:高热休克因子1对高度恶性肿瘤的贡献

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近日,怀特黑德研究所研究人员发现,一个特定的基因表达增加后会促进<a href="http://www.bioon.com/Search.asp?Field=Title&amp;ClassID=&amp;keyword=乳腺癌">乳腺癌</a>、结肠癌和肺癌患者的转移和死亡。这一发现不仅有助于科学家识别基因表达图谱预测患者的治疗效果和治疗...
近日,怀特黑德研究所研究人员发现,一个特定的基因表达增加后会促进<a href="http://www.bioon.com/Search.asp?Field=Title&amp;ClassID=&amp;keyword=乳腺癌">乳腺癌</a>、结肠癌和肺癌患者的转移和死亡。这一发现不仅有助于科学家识别基因表达图谱预测患者的治疗效果和治疗反应,也可以引导开发针对多种类型癌症的疗法。
<p align="center"><img src="http://www.bioon.com/biology/UploadFiles/201208/2012080321513432.jpg" alt="" width="375" height="375" border="0" /></p>
在正常细胞中,各种压力包括热、缺氧、毒素会激活热休克因子1(HSF1),导致所谓的热休克或伴侣蛋白质表达增加,以保持应激细胞内稳态。科学家们已经知道许多癌细胞具有更高水平的伴侣蛋白,这些蛋白质是肿瘤细胞生存和增殖的重要因素。

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然而现在,研究人员报告称HSF1不仅增加癌症伴侣蛋白表达,同时调节范围相当广泛,对肿瘤细胞的恶性行为也有调控作用。HSF1的活性会促进三个最普遍癌症类型:乳腺癌、肺癌、结肠癌的发展。这项研究结果发表在<em>Cell</em>杂志上。

除了证实这种基因激活程序与热休克蛋白不同,研究人员发现,在许多肿瘤中,它在几乎所有肿瘤细胞中会变得活跃。

这说明它不是简单地在肿瘤遭遇环境压力情况下,驱动HSF1的活性,而是连接到HSF1激活癌细胞的核心区域,促发一个独特的基因调控程序,使得肿瘤获得侵略性表型。这表明HSF1本身可能是一个潜在的治疗靶标。

编译自:<a title="" href="http://www.eurekalert.org/pub_releases/2012-08/wifb-hfr073112.php" target="_blank">Heat-shock factor reveals its unique role in supporting highly malignant cancers</a>
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<img src="http://www.bioon.com/biology/UploadFiles/201208/2012080321494653.gif" alt="" width="115" height="150" border="0" />

<a title="" href="http://dx.doi.org/10.1016/j.cell.2012.06.031" target="_blank">doi:10.1016/j.cell.2012.06.031</a>
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<br/><strong>HSF1 Drives a Transcriptional Program Distinct from Heat Shock to Support Highly Malignant Human Cancers</strong><br/>


Marc L. Mendillo, Sandro Santagata, Martina Koeva, George W. Bell, Rong Hu, Rulla M. Tamimi, Ernest Fraenkel, et al.

Heat-Shock Factor 1 (HSF1), master regulator of the heat-shock response, facilitates malignant transformation, cancer cell survival, and proliferation in model systems. The common assumption is that these effects are mediated through regulation of heat-shock protein (HSP) expression. However, the transcriptional network that HSF1 coordinates directly in malignancy and its relationship to the heat-shock response have never been defined. By comparing cells with high and low malignant potential alongside their nontransformed counterparts, we identify an HSF1-regulated transcriptional program specific to highly malignant cells and distinct from heat shock. Cancer-specific genes in this program support oncogenic processes: cell-cycle regulation, signaling, metabolism, adhesion and translation. HSP genes are integral to this program, however, many are uniquely regulated in malignancy. This HSF1 cancer program is active in breast, colon and lung tumors isolated directly from human patients and is strongly associated with metastasis and death. Thus, HSF1 rewires the transcriptome in tumorigenesis, with prognostic and therapeutic implications.

<br/>来源:生物谷

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