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TRP2对p53的调控在黑色素瘤中并不普遍。

p53 regulation by TRP2 is not pervasive in melanoma.

作者信息

Houben Roland, Schmid Corinna P, Maier Melissa, Wobser Marion, Motschenbacher Stephanie, Becker Jürgen C, Vetter-Kauczok Claudia S, Weyandt Gerhard, Hesbacher Sonja, Haferkamp Sebastian

机构信息

Department of Dermatology, Venereology and Allergology, University Hospital Würzburg, Würzburg, Germany.

Department of General Dermatology, Medical University of Graz, Graz, Austria.

出版信息

PLoS One. 2014 Jan 27;9(1):e87440. doi: 10.1371/journal.pone.0087440. eCollection 2014.

Abstract

p53 is a central tumor suppressor protein and its inhibition is believed to be a prerequisite for cancer development. In approximately 50% of all malignancies this is achieved by inactivating mutations in the p53 gene. However, in several cancer entities, including melanoma, p53 mutations are rare. It has been recently proposed that tyrosinase related protein 2 (TRP2), a protein involved in melanin synthesis, may act as suppressor of the p53 pathway in melanoma. To scrutinize this notion we analyzed p53 and TRP2 expression by immunohistochemistry in 172 melanoma tissues and did not find any correlation. Furthermore, we applied three different TRP2 shRNAs to five melanoma cell lines and could not observe a target specific effect of the TRP2 knockdown on either p53 expression nor p53 reporter gene activity. Likewise, ectopic expression of TRP2 in a TRP2 negative melanoma cell line had no impact on p53 expression. In conclusion our data suggest that p53 repression critically controlled by TRP2 is not a general event in melanoma.

摘要

p53是一种核心肿瘤抑制蛋白,其抑制作用被认为是癌症发展的先决条件。在所有恶性肿瘤中,约50%是通过p53基因的失活突变来实现的。然而,在包括黑色素瘤在内的几种癌症实体中,p53突变很少见。最近有人提出,酪氨酸酶相关蛋白2(TRP2),一种参与黑色素合成的蛋白,可能在黑色素瘤中作为p53通路的抑制剂。为了仔细研究这一观点,我们通过免疫组织化学分析了172例黑色素瘤组织中的p53和TRP2表达,未发现任何相关性。此外,我们将三种不同的TRP2短发夹RNA应用于五种黑色素瘤细胞系,未观察到TRP2敲低对p53表达或p53报告基因活性的靶向特异性作用。同样,在TRP2阴性的黑色素瘤细胞系中异位表达TRP2对p53表达也没有影响。总之,我们的数据表明,TRP2对p53的抑制在黑色素瘤中并非普遍现象。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1afd/3903882/0bef686f8666/pone.0087440.g001.jpg

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