The small heat shock protein αA-crystallin is expressed in pancreas and acts as a negative regulator of carcinogenesis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1802

Article

Deng, Mi¹  Chen, Pei-Chao²  Xie, Sisi²  Zhao, Junqiong²  Gong, Lili¹  Liu, Jinping¹  Zhang, Lan^1,2  Sun, Shuming^1,2  Liu, Jiao^1,2  Ma, Haili¹  Batra, Surinder K.¹  Li, David Wan-Cheng^1,2,3 

[1] Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA

[2] Hunan Normal Univ, Coll Life Sci, Natl Educ Minist China, Key Lab Prot Chem & Dev Biol, Changsha 410081, Hunan, Peoples R China

[3] Univ Nebraska, Med Ctr, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA

关键词: Small heat shock protein;    alpha A;    Pancreas;    AP-1;    Smad2/3/5;    TGF beta;    Pancreatic cancer;    Cell migration;    Lens;   

DOI  :  10.1016/j.bbadis.2010.04.004

来源: Elsevier

【 摘 要 】

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.

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