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

The small heat shock protein αA-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 αA-crystallin is found in other tissues including thymus and spleen. In the present study, we have re-examined the distribution of αA-crystallin in various normal human and mouse tissues and found that the normal pancreas expresses a moderate level of αA-crystallin. Moreover, αA-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 αA-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 TGFβ pathway. Finally, expression of αA-crystallin in a pancreatic cancer cell line, MiaPaCa, results in retarded cell migration. Together, these results suggest that αA-crystallin seems to negatively regulate pancreatic carcinogenesis.