Sex Determining Region Y Box 9 Induces Chemoresistance in Pancreatic Cancer Cells by Induction of Putative Cancer Stem Cell Characteristics and Its High Expression Predicts Poor Prognosis

Sex Determining Region Y Box 9 Induces Chemoresistance in Pancreatic Cancer Cells by Induction of... Objectives Pancreatic cancer is a highly chemoresistant tumor and underlying mechanisms are not well understood. Sex determining region Y box 9 (Sox9) is a transcription factor playing important roles on maintenance of pluripotent cells during pancreatic organogenesis. The purpose of this study is to evaluate the roles of Sox9 in pancreatic cancer. Methods The Sox9 expression was evaluated by immunohistochemical analysis. Effects of Sox9 inhibition by siRNA or shRNA on chemosensitivity, sphere formation, stem cell markers expression, and in vivo tumor formation rate were examined using pancreatic cancer cell lines. Results High expression of Sox9 in pancreatic cancer tissue is correlated with poor prognosis (P = 0.011). Cells with high Sox9 expression (PANC-1, Capan-1) showed stronger chemoresistance to Gemcitabine than cells with low Sox9 expression (BxPC-3, MiaPaCa-2). The chemosensitivity in PANC-1 was recovered by suppressing Sox9 using siRNA (P < 0.05). Both sphere formation rate and the proportion of CD44highCD24high cells were decreased by Sox9 inhibition. Tumor formation rate of Tet-on inducible Sox9 shRNA-transfected PANC-1 cells in KSN/Slc nude mice was decreased by induction of shRNA with doxycycline feeding (P < 0.05). Conclusion Sox9 plays an important role in chemoresistance by the induction of stemness in pancreatic cancer cells. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pancreas Wolters Kluwer Health

Sex Determining Region Y Box 9 Induces Chemoresistance in Pancreatic Cancer Cells by Induction of Putative Cancer Stem Cell Characteristics and Its High Expression Predicts Poor Prognosis

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Publisher
Wolters Kluwer Health
Copyright
Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
ISSN
0885-3177
eISSN
1536-4828
D.O.I.
10.1097/MPA.0000000000000945
Publisher site
See Article on Publisher Site

Abstract

Objectives Pancreatic cancer is a highly chemoresistant tumor and underlying mechanisms are not well understood. Sex determining region Y box 9 (Sox9) is a transcription factor playing important roles on maintenance of pluripotent cells during pancreatic organogenesis. The purpose of this study is to evaluate the roles of Sox9 in pancreatic cancer. Methods The Sox9 expression was evaluated by immunohistochemical analysis. Effects of Sox9 inhibition by siRNA or shRNA on chemosensitivity, sphere formation, stem cell markers expression, and in vivo tumor formation rate were examined using pancreatic cancer cell lines. Results High expression of Sox9 in pancreatic cancer tissue is correlated with poor prognosis (P = 0.011). Cells with high Sox9 expression (PANC-1, Capan-1) showed stronger chemoresistance to Gemcitabine than cells with low Sox9 expression (BxPC-3, MiaPaCa-2). The chemosensitivity in PANC-1 was recovered by suppressing Sox9 using siRNA (P < 0.05). Both sphere formation rate and the proportion of CD44highCD24high cells were decreased by Sox9 inhibition. Tumor formation rate of Tet-on inducible Sox9 shRNA-transfected PANC-1 cells in KSN/Slc nude mice was decreased by induction of shRNA with doxycycline feeding (P < 0.05). Conclusion Sox9 plays an important role in chemoresistance by the induction of stemness in pancreatic cancer cells.

Journal

PancreasWolters Kluwer Health

Published: Mar 1, 2017

References

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