Wagner P, Wang B, Clark E, Lee H, Rouzier R, Pusztai L
Deparment of Breast Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77230-1439, USA.
Cell Cycle. 2005 Sep;4(9):1149-52. doi: 10.4161/cc.4.9.2038. Epub 2005 Sep 17.
Microtubule binding protein Tau was recently identified through gene expression analysis of human breast cancer tissues as a novel marker of response to paclitaxel. This article reviews these recent findings and provides additional information to support the role of Tau as an emerging marker and mediator of paclitaxel sensitivity. Low expression of Tau is associated with increased sensitivity to paclitaxel in human breast cancer as well as in a broad range of cell lines. Down regulation of Tau in cell lines by siRNA increases their sensitivity to paclitaxel but not to anthracycline chemotherapy. We propose that this is due to increased paclitaxel binding to microtubules when microtubules are assembled in the presence of low concentrations (or absence) of Tau compared to microtubules that are formed in the presence of physiological (or higher) levels of Tau.
微管结合蛋白Tau最近通过对人类乳腺癌组织的基因表达分析被鉴定为对紫杉醇反应的一种新标志物。本文回顾了这些最新发现，并提供了更多信息来支持Tau作为紫杉醇敏感性的新兴标志物和介质的作用。Tau的低表达与人类乳腺癌以及广泛的细胞系中对紫杉醇的敏感性增加有关。通过小干扰RNA（siRNA）在细胞系中下调Tau会增加它们对紫杉醇的敏感性，但对蒽环类化疗药物不敏感。我们认为，这是由于与在生理（或更高）水平的Tau存在下形成的微管相比，当微管在低浓度（或不存在）Tau的情况下组装时，紫杉醇与微管的结合增加。
