hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer

Franklin, Renty B.; Feng, Peng; Milon, Béatrice; Desouki, Mohamed Mokhtar; Singh, Keshav K.; Kajdacsy-Balla, André; Bagasra, Omar; Costello, Leslie C.

doi:10.1186/1476-4598-4-32

Cited by 221 publications

(162 citation statements)

References 39 publications

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“…Developmentally regulated changes in expression of some ZnT genes have been reported (9). Zip1 in prostate is regulated by prolactin and testosterone and may contribute to the atypically high zinc in the prostatic epithelium (52). Zip1 is markedly reduced in the malignant prostate and correlates with concomitantly lower zinc concentration in the malignant cells.…”

Section: Transporter Regulationmentioning

confidence: 97%

Mammalian Zinc Transport, Trafficking, and Signals

Cousins

Liuzzi

Lichten

2006

Journal of Biological Chemistry

604

461

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Section: Transporter Regulationmentioning

confidence: 97%

Mammalian Zinc Transport, Trafficking, and Signals

Cousins

Liuzzi

Lichten

2006

Journal of Biological Chemistry

604

461

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“…It is now established that the zinc transporter, ZIP1, is responsible for zinc uptake and accumulation in prostate cells [11,12]. Recent studies using prostate tissue sections have revealed the expression of ZIP1 and high cellular zinc levels in citrate-producing non-malignant prostate glands [13]. In contrast, adjacent malignant glands exhibited down-regulation of ZIP1 gene expression and transporter protein level and depletion of zinc.…”

Section: Zinc Transport and Metabolic Relationships In Prostate Cellumentioning

confidence: 98%

Zinc as an anti-tumor agent in prostate cancer and in other cancers

Franklin¹,

Costello²

2007

Archives of Biochemistry and Biophysics

207

139

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Human prostate glandular epithelial cells have the unique capability of accumulating high levels of zinc. This is essential to inhibit m-aconitase activity so that citrate can accumulate for secretion into prostatic fluid, which is a major function of the prostate gland. As a result, the Krebs cycle is truncated with the consequence of the lost ATP production that would result from citrate oxidation. The cellular accumulation of zinc also inhibits mitochondrial terminal oxidation and respiration. In addition to these metabolic effects, zinc accumulation exhibits anti-proliferative effects via its induction of mitochondrial apoptogenesis. Zinc accumulation also inhibits the invasive/migration activities in malignant prostate cells. The anti-proliferative effects and the effects on invasion and migration occur through zinc activation of specific intracellular signaling pathways. Consequently, these effects impose anti-tumor actions by zinc. The ability of prostate cells to accumulate zinc is due to the expression and activity of the zinc uptake transporter, ZIP1. To avoid the anti-tumor effects of zinc, in prostate cancer the malignant prostate cells exhibit a silencing of ZIP1 gene expression accompanied by a depletion of cellular zinc. Therefore we regard ZIP1 as a tumor suppressor gene in prostate cancer. In addition to prostate cells, similar tumor suppressor effects of zinc have been identified in several other types of tumors. KeywordsZinc; prostate cancer; tumor suppressor; apoptosis; Krebs cycle; zinc transporter; intermediary metabolismThe physiology and biochemistry of zinc and its importance in normal cellular and bodily function has been the subject of numerous reviews [1][2][3][4]. The regulation and maintenance of a "normal" concentration and distribution of cellular zinc are essential to the function, metabolism, growth, proliferation and survival of cells. A significant clinical aspect of zinc is its role in the development and progression of malignancy. There is now compelling clinical and experimental evidence that zinc is an important factor in prostate cancer, and also in other types of cancer. In relation to essential tumor cell activities, the effects of zinc can be categorized as: intermediary metabolism and bioenergetics effects; motility and invasive effects; growth and proliferation effects. The actions of zinc on all three activities impose antitumor effects in malignant prostate cells and other tumor cells. This review will present the *Correspondence to: Renty B.

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“…Silencing of the expression of zinc transporters (hZIP1-3) is an early event in the development of PCa and these proteins are required to maintain high zinc concentrations in prostate tissue and suppress cis-aconitase and presumably mitochondrial activity ( Fig. 1; Franklin et al 2005, Desouki et al 2007). Other early changes involve promoter hypermethylation and repressed transcription of antioxidant enzymes of the glutathione S-transferase family (Tokumaru et al 2004).…”

Section: Defining Clinically Relevant Ar Target Genes and Pathwaysmentioning

confidence: 99%

Androgen-regulated metabolism and biosynthesis in prostate cancer

Barfeld¹,

Itkonen²,

Urbanucci³

et al. 2014

Endocrine-Related Cancer

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Metabolic changes are a well-described hallmark of cancer and are responses to changes in the activity of diverse oncogenes and tumour suppressors. For example, steroid hormone biosynthesis is intimately associated with changes in lipid metabolism and represents a therapeutic intervention point in the treatment of prostate cancer (PCa). Both prostate gland development and tumorigenesis rely on the activity of a steroid hormone receptor family member, the androgen receptor (AR). Recent studies have sought to define the biological effect of the AR on PCa by defining the whole-genome binding sites and gene networks that are regulated by the AR. These studies have provided the first systematic evidence that the AR influences metabolism and biosynthesis at key regulatory steps within pathways that have also been defined as points of influence for other oncogenes, including c-Myc, p53 and hypoxia-inducible factor 1a, in other cancers. The success of interfering with these pathways in a therapeutic setting will, however, hinge on our ability to manage the concomitant stress and survival responses induced by such treatments and to define appropriate therapeutic windows.

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hZIP1 zinc uptake transporter down regulation and zinc depletion in prostate cancer

Cited by 221 publications

References 39 publications

Mammalian Zinc Transport, Trafficking, and Signals

Mammalian Zinc Transport, Trafficking, and Signals

Zinc as an anti-tumor agent in prostate cancer and in other cancers

Androgen-regulated metabolism and biosynthesis in prostate cancer

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