title: High glucose level promotes migration behavior of breast cancer cells through zinc and its transporters.
abstract: BACKGROUND
  The diabetes patients have been associated with an increased risk of mortality by breast cancer and there are difference between the breast cancer patients with diabetes, and their nondiabetic counterparts in the regimen choice and effects of breast cancer treatment. However, the pathophysiological relationships of diabetes and breast cancer have not yet been elucidated in detail. In this study, we investigate the breast cancer cell line, MCF-7 motility, which linked to invasion and metastasis, in high glucose level corresponding to hyperglycemia and the role of Zn and its transporter.
  
  
  RESULTS
  We demonstrated the significant motility of MCF-7 cultured in hyperglycemic level (25 mM glucose) in comparison to normal physiological glucose level (5.5 mM glucose). The other hand, the osmotic control medium, 5.5 mM glucose with 19.5 mM mannitol or fructose had no effect on migratory, suggesting that high glucose level promotes the migration of MCF-7. Moreover, the activity of intracellular Zn(2+) uptake significantly increased in high glucose-treated cells in comparison to 5.5 mM glucose, and the mRNA expression of zinc transporters, ZIP6 and ZIP10, was upregulated in 25 mM glucose-treated cells. The deficiency of ZIP6 or ZIP10 and intracellular Zn(2+) significantly inhibited the high migration activity in 25 mM glucose medium, indicating that Zn(2+) transported via ZIP6 and ZIP10 play an essential role in the promotion of cell motility by high glucose stimulation.
  
  
  CONCLUSIONS
  Zinc and its transporters, ZIP6 and ZIP10, are required for the motility stimulated with high glucose level. These findings provide the first evidence proposing the novel strategies for the diagnosis and therapy of breast cancer with hyperglycemia.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Tomoka
authors.initials: T
authors.lastname: Takatani-Nakase
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Matsui
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Sachie
authors.initials: S
authors.lastname: Maeda
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Kawahara
authors.affiliation: Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Hyogo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D027682:Cation Transport Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D017136:Ion Transport / Q000187:drug effects; D042361:Mammary Glands, Human / Q000378:metabolism / Q000473:pathology; D008353:Mannitol / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D009994:Osmolar Concentration; D012333:RNA, Messenger / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
chemical_list: D027682:Cation Transport Proteins; D002413:Cations, Divalent; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C519886:SLC39A10 protein, human; C418627:SLC39A6 protein, human; D008353:Mannitol; D005947:Glucose; D015032:Zinc