The small heat shock protein alphaA-crystallin is expressed in pancreas and acts as a negative regulator of carcinogenesis.
The small heat shock protein alphaA-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 alphaA-crystallin is found in other tissues including thymus and spleen. In the present study, we have re-examined the distribution of alphaA-crystallin in various normal human and mouse tissues and found that the normal pancreas expresses a moderate level of alphaA-crystallin. Moreover, alphaA-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 alphaA-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 TGFbeta pathway. Finally, expression of alphaA-crystallin in a pancreatic cancer cell line, MiaPaCa, results in retarded cell migration. Together, these results suggest that alphaA-crystallin seems to negatively regulate pancreatic carcinogenesis.
Deng
Mi
M
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA.
Chen
Pei-Chao
PC
Xie
Sisi
S
Zhao
Junqiong
J
Gong
Lili
L
Liu
Jinping
J
Zhang
Lan
L
Sun
Shuming
S
Liu
Jiao
J
Ma
Haili
H
Batra
Surinder K
SK
Li
David Wan-Cheng
DW
D000818:Animals; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D019610:Cytoprotection / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051379:Mice; D008970:Molecular Weight; D010179:Pancreas / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured; D038202:alpha-Crystallin A Chain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D006360:Heat-Shock Proteins; D038202:alpha-Crystallin A Chain