Abstract

BackgroundThe 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.Methodology/Principal findingsWe 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 Zn2+ 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 Zn2+ significantly inhibited the high migration activity in 25 mM glucose medium, indicating that Zn2+ transported via ZIP6 and ZIP10 play an essential role in the promotion of cell motility by high glucose stimulation.Conclusion/SignificanceZinc 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.

Highlights

  • The statistical result analysis of diabetes and breast cancer has indicated that the diabetes has been associated with an increased risk of mortality by breast cancer [1,2,3]

  • We demonstrated that breast cancer cell line, MCF-7 cultured with high glucose level corresponding to hyperglycemia, significantly promoted migratory activity compared with normal physiological glucose level, indicating the possibility that the hyperglycemia in diabetes mediates the motility of breast cancer cells

  • The osmotic control medium, 5.5 mM glucose with 19.5 mM mannitol or fructose had no effect on migratory rate, suggesting that high glucose level promotes the migration of MCF-7

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Summary

Introduction

The statistical result analysis of diabetes and breast cancer has indicated that the diabetes has been associated with an increased risk of mortality by breast cancer [1,2,3]. It has been reported that there are difference between the breast cancer patients with diabetes and their nondiabetic counterparts in the regimen choice and effects of breast cancer treatment [1,2,4]. We demonstrated that breast cancer cell line, MCF-7 cultured with high glucose level corresponding to hyperglycemia, significantly promoted migratory activity compared with normal physiological glucose level, indicating the possibility that the hyperglycemia in diabetes mediates the motility of breast cancer cells. 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. 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

Methods
Results
Conclusion
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