DEPTOR has growth suppression activity against pancreatic cancer cells
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Hua Li1, Grace Y. Sun1, Yongchao Zhao1, Dafydd Thomas2, Joel K. Greenson2, Mark M. Zalupski3, Edgar Ben-Josef1, Yi Sun1,4
1Division of Radiation and Cancer Biology, Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA
2Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA
3Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
4Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang, P.R. China
Keywords: DEPTOR, mTOR pathway, pancreatic cancer, growth suppression
Received: August 26, 2014 Accepted: October 27, 2014 Published: December 30, 2014
DEPTOR was reported as a naturally occurring inhibitor of mTORC1 and mTORC2. The role of DEPTOR in the growth and survival of pancreatic cancer cells has not previously been determined. Here we report that while DEPTOR shows a cytoplasmic expression in both normal pancreatic acinar and islet cells in a patchy manner, its expression is reduced in PanIN1 and PanIN2 and completely lost in 100 out of 101 pancreatic ductal adenocarcinoma (PDAC) tissues. Ectopic DEPTOR expression in two pancreatic cancer cell lines, Panc-1 and Miapaca-2, caused a significant 1) suppression of anchorage-dependent growth in monolayer culture, particularly under conditions with growth factor deprivation; 2) decreased clonogenic survival, and 3) suppressed anchorage-independent growth in soft agar. These effects are attributable to moderate induction of apoptosis and growth arrest at the S and G2/M phases, in a cell line dependent manner. Furthermore, ectopic DEPTOR expression moderately inhibited mTORC1 activity, as demonstrated by reduced phosphorylation of S6K, S6, and 4E-BP1. Taken together, these data suggest that DEPTOR has a tumor suppressive activity against pancreatic cancer cells, and its loss of expression may contribute to pancreatic tumorigenesis.
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