The small heat shock protein αA-crystallin is expressed in pancreas and acts as a negative regulator of carcinogenesis
The small heat shock protein αA-crystallin is expressed in pancreas and acts as a negative regulator of carcinogenesis
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DOI：
10.1016/j.bbadis.2010.04.004
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发表时间：
2010-07-01
影响因子：
6.2
通讯作者：
Li, David Wan-Cheng
中科院分区：
文献类型：
--
作者：
Deng, Mi;Chen, Pei-Chao;Li, David Wan-Cheng
小热休克蛋白α A-晶状体蛋白是眼透镜中的结构蛋白。此外，最近的研究还发现它是一种分子伴侣、一种自激酶和一种强的抗凋亡调节剂。除了其透镜状分布外，先前的研究表明，在其他组织（包括胸腺和脾脏）中发现了可检测水平的α A-晶状体蛋白。在本研究中，我们重新检查了α A-晶状体蛋白在各种正常人和小鼠组织中的分布，发现正常胰腺表达中等水平的α A-晶状体蛋白。此外，在60例不同类型的胰腺癌中发现α A-晶体蛋白比11例正常人胰腺样品中显著下调。此外，我们证明α A-晶状体蛋白可以通过调节MAP激酶的功能来增强激活蛋白-1（AP-1）的活性，并且还上调TGF β途径的组分。最后，α A-晶体蛋白在胰腺癌细胞系MiaPaCa中的表达导致细胞迁移延迟。总之，这些结果表明，α A-晶体蛋白似乎负调控胰腺癌的发生。(C)2010 Elsevier B. V.保留所有权利。
The small heat shock protein alpha A-crystallin is a structural protein in the ocular lens. In addition, recent studies have also revealed that it is a molecular chaperone, an autokinase and a strong anti-apoptotic regulator. Besides its lenticular distribution, a previous study demonstrates that a detectable level of alpha A-crystallin is found in other tissues including thymus and spleen. In the present study, we have re-examined the distribution of alpha A-crystallin in various normal human and mouse tissues and found that the normal pancreas expresses a moderate level of alpha A-crystallin. Moreover, alpha A-crystallin is found significantly downregulated in 60 cases of pancreatic carcinoma of different types than it is in 11 normal human pancreas samples. In addition, we demonstrate that alpha A-crystallin can enhance the activity of the activating protein-1 (AP-1) through modulating the function of the MAP kinase, and also upregulates components of TGF beta pathway. Finally, expression of alpha A-crystallin in a pancreatic cancer cell line, MiaPaCa, results in retarded cell migration. Together, these results suggest that alpha A-crystallin seems to negatively regulate pancreatic carcinogenesis. (C) 2010 Elsevier B.V. All rights reserved.