title: PKC?-dependent activation of the ubiquitin proteasome system is responsible for high glucose-induced human breast cancer MCF-7 cell proliferation, migration and invasion.
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?)-phosphorylation. Administration of the specific PKC? inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, PKC? inhibition by both rottlerin and PKC? shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that PKC?-dependent ubiquitin proteasome system activation plays an important role in high glucose- induced breast cancer cell growth and metastasis.
authors.affiliation: Department of Breast and Thyroid Surgery, Renmin Hospital of Wuhan University, Wuhan, China E-mail : sun137@sina.com.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhu
authors.forename: Feng
authors.initials: F
authors.lastname: Yao
authors.forename: Wen-Huan
authors.initials: WH
authors.lastname: Li
authors.forename: Jin-Nan
authors.initials: JN
authors.lastname: Wan
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zhang
authors.forename: Zhao
authors.initials: Z
authors.lastname: Tang
authors.forename: Shahzad
authors.initials: S
authors.lastname: Khan
authors.forename: Chang-Hua
authors.initials: CH
authors.lastname: Wang
authors.forename: Sheng-Rong
authors.initials: SR
authors.lastname: Sun
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology; D001897:Boronic Acids / Q000494:pharmacology; D000069286:Bortezomib; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation / Q000187:drug effects; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000494:pharmacology; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011719:Pyrazines / Q000494:pharmacology; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D000098:Acetophenones; D001578:Benzopyrans; D001897:Boronic Acids; D061988:Proteasome Inhibitors; D011719:Pyrazines; D025801:Ubiquitin; D000069286:Bortezomib; C085746:rottlerin; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta; D046988:Proteasome Endopeptidase Complex; D005947:Glucose