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Nutrients 2012, 4(8), 875-903; doi:10.3390/nu4080875
Review

Cellular Mechanisms of Zinc Dysregulation: A Perspective on Zinc Homeostasis as an Etiological Factor in the Development and Progression of Breast Cancer

1
 and 1,2,3,*
Received: 29 May 2012; in revised form: 11 July 2012 / Accepted: 17 July 2012 / Published: 30 July 2012
(This article belongs to the Special Issue Zinc in Health and Disease)
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Abstract: Worldwide, breast cancer is the most commonly diagnosed cancer among women and is the leading cause of female cancer deaths. Zinc (Zn) functions as an antioxidant and plays a role in maintaining genomic stability. Zn deficiency results in oxidative DNA damage and increased cancer risk. Studies suggest an inverse association between dietary and plasma Zn levels and the risk for developing breast cancer. In contrast, breast tumor biopsies display significantly higher Zn levels compared with normal tissue. Zn accumulation in tumor tissue also correlates with increased levels of Zn importing proteins. Further, aberrant expression of Zn transporters in tumors correlates with malignancy, suggesting that altered metal homeostasis in the breast could contribute to malignant transformation and the severity of cancer. However, studies have yet to link dysregulated Zn transport and abnormal Zn-dependent functions in breast cancer development. Herein, we summarize studies that address the multi-modal role of Zn dyshomeostasis in breast cancer with respect to the role of Zn in modulating oxidative stress, DNA damage response/repair pathways and cell proliferation/apoptosis, and the relationship to aberrant regulation of Zn transporters. We also compare Zn dysregulation in breast tissue to that of prostate, pancreatic and ovarian cancer where possible.
Keywords: breast cancer; zinc homeostasis; oxidative stress; DNA damage/repair; transcription; zinc transport; cell cycle; proliferation; cell signaling; apoptosis breast cancer; zinc homeostasis; oxidative stress; DNA damage/repair; transcription; zinc transport; cell cycle; proliferation; cell signaling; apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Alam, S.; Kelleher, S.L. Cellular Mechanisms of Zinc Dysregulation: A Perspective on Zinc Homeostasis as an Etiological Factor in the Development and Progression of Breast Cancer. Nutrients 2012, 4, 875-903.

AMA Style

Alam S, Kelleher SL. Cellular Mechanisms of Zinc Dysregulation: A Perspective on Zinc Homeostasis as an Etiological Factor in the Development and Progression of Breast Cancer. Nutrients. 2012; 4(8):875-903.

Chicago/Turabian Style

Alam, Samina; Kelleher, Shannon L. 2012. "Cellular Mechanisms of Zinc Dysregulation: A Perspective on Zinc Homeostasis as an Etiological Factor in the Development and Progression of Breast Cancer." Nutrients 4, no. 8: 875-903.


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