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鉴定一种人β V-微管蛋白抗体,并在正常和恶性人组织中表达这种同种型。

Characterization of a human βV-tubulin antibody and expression of this isotype in normal and malignant human tissue.

机构信息

Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.

出版信息

Cytoskeleton (Hoboken). 2012 Aug;69(8):566-76. doi: 10.1002/cm.21043. Epub 2012 Jul 2.

Abstract

There are seven distinct β-tubulin isotypes and eight α-tubulin isotypes in mammals that are hypothesized to have tissue- and cell-specific functions. There is an interest in the use of tubulin isotypes as prognostic markers of malignancy. βV-tubulin, like βIII-tubulin, has been implicated in malignant transformation and drug resistance, however little is known about its localization and function. Thus, we generated for the first time, a rabbit polyclonal antibody specific for human βV-tubulin. The antibody did not cross-react with mouse βV-tubulin or other human β-tubulin isotypes and specifically labeled βV-tubulin by immunoblotting, immunofluorescence and immunohistochemistry. Immunohistochemistry of various human normal tissues revealed that βV-tubulin was expressed in endothelial cells, myocytes and cells with muscle differentiation, structures with transport and/or secretory function such as renal tubules, pancreatic ducts and bile ducts, and epithelium with secretory function such as prostate. βV-tubulin was also specifically expressed in pancreatic islets and intratubular germ cell neoplasia, where it may have diagnostic utility. Initial studies in breast, lung and ovarian cancers indicated aberrant expression of βV-tubulin, suggesting that this isoform may be associated with tumorigenesis. Thus, βV-tubulin expression is a potentially promising prognostic marker of malignancy.

摘要

哺乳动物中有七种不同的β-微管蛋白同工型和八种α-微管蛋白同工型,它们被认为具有组织和细胞特异性功能。人们对将微管蛋白同工型用作恶性肿瘤的预后标志物很感兴趣。βV-微管蛋白与βIII-微管蛋白一样,与恶性转化和耐药性有关,但对其定位和功能知之甚少。因此,我们首次生成了一种针对人βV-微管蛋白的兔多克隆抗体。该抗体不会与小鼠βV-微管蛋白或其他人类β-微管蛋白同工型发生交叉反应,并且通过免疫印迹、免疫荧光和免疫组织化学特异性标记βV-微管蛋白。对各种人类正常组织的免疫组织化学分析表明,βV-微管蛋白在血管内皮细胞、心肌细胞和具有肌肉分化的细胞、具有运输和/或分泌功能的结构(如肾小管、胰腺导管和胆管)以及具有分泌功能的上皮细胞中表达。βV-微管蛋白还在胰腺胰岛和管内生殖细胞肿瘤中特异性表达,这可能具有诊断效用。在乳腺癌、肺癌和卵巢癌的初步研究中,βV-微管蛋白的表达异常,表明该同工型可能与肿瘤发生有关。因此,βV-微管蛋白的表达是一种有前途的恶性肿瘤预后标志物。

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