The same result was found in vivo. Those results indicate that mesothelin silencing promoted apoptosis through p53-independent

pathway in cells with null/mt-p53. In addition to p53, a number of other transcription factors are implicated in PUMA induction. The p53 homologue p73 can regulate PUMA expression independent of p53 by binding buy CHIR-99021 to the same p53-responsive elements in the PUMA promoter in response to a variety of stimuli [33, 34]. On the other hand, PUMA transcription is subject to negative regulation by transcriptional repressors, including Slug [35].In the present study,whether PUMA was regulated by other factors need further investigation. Conclusion The present findings provide evidence of a novel biological function for mesothelin and a mechanism by which mesothelin ptomotes proliferation and inhibited apoptosis through p53-dependent pathway in pancreatic cancer cells with wt-p53, and p53-independent pathway in pancreatic cancer cells with mt-p53 or null-p53. Those results indicate that mesothelin is an important factor in pancreatic cancer growth and a potential target

for pancreatic cancer treatment. The significant reduction in pancreatic cancer growth by mesothelin shRNA indicated STI571 the importance of shRNA blockage and CDK inhibitor opened a door for shRNA pancreatic cancer therapy that targets MSLN. Acknowledgements This work was supported by the National Institutes of Health Grant (No:TK2011-037-A6). References 1. Matthaios D, Zarogoulidis

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