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      Zinc and Cancer: Implications for LIV-1 in Breast Cancer

      review-article
      Author(s): 1 , * , 2 , *
      Publication date (Electronic):
      Journal: Nutrients
      Publisher: MDPI
      Keywords: zinc, zinc transporters, cancer, LIV-1, ZIP6

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          Abstract

          Zinc is a trace mineral which is vital for the functioning of numerous cellular processes, is critical for growth, and may play an important role in cancer etiology and outcome. The intracellular levels of this mineral are regulated through the coordinated expression of zinc transporters, which modulate both zinc influx as well as efflux. LIV-1 (ZIP6) was first described in 1988 as an estrogen regulated gene with later work suggesting a role for this transporter in cancer growth and metastasis. Despite evidence of its potential utility as a target gene for cancer prognosis and treatment, LIV-1 has received relatively little attention, with only three prior reviews being published on this topic. Herein, the physiological effects of zinc are reviewed in light of this mineral’s role in cancer growth with specific attention being given to LIV-1 and the potential importance of this transporter to breast cancer etiology.

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          IFNgamma and lymphocytes prevent primary tumour development and shape tumour immunogenicity.

          V Shankaran, H. Ikeda, A. T. Bruce … (2001)
          Lymphocytes were originally thought to form the basis of a 'cancer immunosurveillance' process that protects immunocompetent hosts against primary tumour development, but this idea was largely abandoned when no differences in primary tumour development were found between athymic nude mice and syngeneic wild-type mice. However, subsequent observations that nude mice do not completely lack functional T cells and that two components of the immune system-IFNgamma and perforin-help to prevent tumour formation in mice have led to renewed interest in a tumour-suppressor role for the immune response. Here we show that lymphocytes and IFNgamma collaborate to protect against development of carcinogen-induced sarcomas and spontaneous epithelial carcinomas and also to select for tumour cells with reduced immunogenicity. The immune response thus functions as an effective extrinsic tumour-suppressor system. However, this process also leads to the immunoselection of tumour cells that are more capable of surviving in an immunocompetent host, which explains the apparent paradox of tumour formation in immunologically intact individuals.
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            A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1.

            Y Miki, J. Swensen, D Shattuck-Eidens … (1994)
            A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods. Probable predisposing mutations have been detected in five of eight kindreds presumed to segregate BRCA1 susceptibility alleles. The mutations include an 11-base pair deletion, a 1-base pair insertion, a stop codon, a missense substitution, and an inferred regulatory mutation. The BRCA1 gene is expressed in numerous tissues, including breast and ovary, and encodes a predicted protein of 1863 amino acids. This protein contains a zinc finger domain in its amino-terminal region, but is otherwise unrelated to previously described proteins. Identification of BRCA1 should facilitate early diagnosis of breast and ovarian cancer susceptibility in some individuals as well as a better understanding of breast cancer biology.
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              The steroid and thyroid hormone receptor superfamily.

              Ronald Evans (1988)
              Analyses of steroid receptors are important for understanding molecular details of transcriptional control, as well as providing insight as to how an individual transacting factor contributes to cell identity and function. These studies have led to the identification of a superfamily of regulatory proteins that include receptors for thyroid hormone and the vertebrate morphogen retinoic acid. Although animals employ complex and often distinct ways to control their physiology and development, the discovery of receptor-related molecules in a wide range of species suggests that mechanisms underlying morphogenesis and homeostasis may be more ubiquitous than previously expected.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nutrients
                Journal ID (iso-abbrev): Nutrients
                Journal ID (publisher-id): nutrients
                Title: Nutrients
                Publisher: MDPI
                ISSN (Electronic): 2072-6643
                Publication date (Electronic): 04 July 2012
                Publication date Collection: July 2012
                Volume: 4
                Issue: 7
                Pages: 648-675
                Affiliations
                [1 ] Department of Family Medicine, Stony Brook University Hospital Medical Center, Stony Brook, New York, NY 11597, USA
                [2 ] Department of Nutritional Sciences, University of Connecticut, Storrs, CT 06268, USA
                Author notes
                [* ] Authors to whom correspondence should be addressed; Email: bruce.grattan@ 123456stonybrookmedicine.edu (B.J.G.); hedley.freake@ 123456uconn.edu (H.C.F.); Tel.: +1-631-444-8245; Fax: +1-631-444-7552.
                Article
                Publisher ID: nutrients-04-00648
                DOI: 10.3390/nu4070648
                PMC ID: 3407987
                PubMed ID: 22852056
                SO-VID: 7d527b20-d863-4ba6-b121-787b6c184a30
                Copyright © © 2012 by the authors; licensee MDPI, Basel, Switzerland.
                License:

                This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                Date received : 03 May 2012
                Date revision received : 07 June 2012
                Date accepted : 27 June 2012
                Categories
                Subject: Review

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: cancer,zinc transporters,liv-1,zip6,zinc
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: cancer, zinc transporters, liv-1, zip6, zinc

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