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PKCδ-dependent Activation of the Ubiquitin Proteasome System is Responsible for High Glucose-induced Human Breast Cancer MCF-7 Cell Proliferation, Migration and Invasion

  • Zhu, Shan (Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University) ;
  • Yao, Feng (Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University) ;
  • Li, Wen-Huan (Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University) ;
  • Wan, Jin-Nan (Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University) ;
  • Zhang, Yi-Min (Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University) ;
  • Tang, Zhao (Department of Pathology and Pathophysiology, Wuhan University School of Basic Medical Sciences) ;
  • Khan, Shahzad (Department of Pathology and Pathophysiology, Wuhan University School of Basic Medical Sciences) ;
  • Wang, Chang-Hua (Department of Pathology and Pathophysiology, Wuhan University School of Basic Medical Sciences) ;
  • Sun, Sheng-Rong (Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University)
  • Published : 2013.10.30

Abstract

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

Keywords

High glucose;ubiquitin proteasome system;protein kinase C ${\delta}$;breast cancer

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