Research Papers:
Overexpression of ankyrin1 promotes pancreatic cancer cell growth
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Abstract
Noriyuki Omura1, Masamichi Mizuma1, Anne MacGregor1, Seung-Mo Hong1, Michael Ayars1, Jose Alejandro Almario1, Michael Borges1, Mitsuro Kanda1, Ang Li1, Audrey Vincent1, Anirban Maitra1,2, Michael Goggins1,2,3
1Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA
2Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA
3Department of Medicine, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions, Johns Hopkins University, Baltimore, MD, USA
Correspondence to:
Michael Goggins, email: [email protected]
Keywords: pancreatic cancer, ANK1, hypomethylation, ankyrin, mir-486
Received: February 13, 2016 Accepted: April 10, 2016 Published: April 26, 2016
ABSTRACT
The methylation status of a promoter influences gene expression and aberrant methylation during tumor development has important functional consequences for pancreatic and other cancers. Using methylated CpG island amplification and promoter microarrays, we identified ANK1 as hypomethylated in pancreatic cancers. Expression analysis determined ANK1 as commonly overexpressed in pancreatic cancers relative to normal pancreas. ANK1 was co-expressed with miR-486 in pancreatic cancer cells. Stable knockdown of ANK1 in the pancreatic cancer cell line AsPC1 led to changes in cell morphology, and decreases in colony formation. Stable knockdown of ANK1 also marked reduced the growth of tumors in athymic nude mice. Among patients undergoing pancreaticoduodenectomy, those with pancreatic cancers expressing ANK1 had a poorer prognosis than those without ANK1 expression. These findings indicate a role for ANK1 overexpression in mediating pancreatic cancer tumorigenicity.
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