McDowell Christina L, Bryan Sutton R, Obermann Wolfgang M J
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA.
Int J Biol Macromol. 2009 Oct 1;45(3):310-4. doi: 10.1016/j.ijbiomac.2009.06.012. Epub 2009 Jul 1.
The activity of many oncogenic proteins depends on the molecular chaperone Hsp90. Recent studies indicate that tumorigenesis is associated with increased expression of chaperones, such as Hsp90. However, little is known about the isoform dependence and cochaperone contribution on tumor formation. Here we report the first systematic expression profiling for Hsp90alpha and Hsp90beta, the cochaperones Aha1, Cdc37, p23, Tpr2, and the Hsp90 dependent transcription factor HSF1 in a set of different tumor tissue samples. We find that in 10 out of 17 human tumors the expression level of at least one Hsp90 or Hsp90 cochaperone protein is significantly elevated. However, individual tumors show unique patterns of expression. Furthermore, Hsp90alpha and Hsp90beta expression levels are not related. Our results suggest that expression profiling of Hsp90alpha and Hsp90beta and its cochaperone proteins may be useful for cancer diagnosis and prognosis as well as for tailoring of drugs that interfere with the Hsp90 system in a tumor specific manner.
许多致癌蛋白的活性依赖于分子伴侣Hsp90。最近的研究表明，肿瘤发生与伴侣蛋白（如Hsp90）表达增加有关。然而，关于亚型依赖性和共伴侣蛋白对肿瘤形成的作用却知之甚少。在此，我们报告了Hsp90α和Hsp90β、共伴侣蛋白Aha1、Cdc37、p23、Tpr2以及Hsp90依赖性转录因子HSF1在一组不同肿瘤组织样本中的首个系统性表达谱分析。我们发现，在17种人类肿瘤中的10种里，至少一种Hsp90或Hsp90共伴侣蛋白的表达水平显著升高。然而，个别肿瘤呈现出独特的表达模式。此外，Hsp90α和Hsp90β的表达水平并无关联。我们的结果表明，Hsp90α和Hsp90β及其共伴侣蛋白的表达谱分析可能有助于癌症诊断和预后评估，以及以肿瘤特异性方式定制干扰Hsp90系统的药物。
