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Title:   Author  item
                                            Huang, Lipingitem
                                            Kirschke, Catherineitem
                                            ZHANG, YUNFAN - UC DAVIS, NUTRITION DEPT.
  Submitted to: Popular Publication
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 3/31/2006
                                    Publication  Date: 3/31/2006
                                    Citation: Huang, L., Kirschke, C.P., Zhang, Y. Decreased intracellular zinc in human tumorigenic prostate epithelial cells: a possible role in prostate cancer progression. Cancer Cell International 2006, 6:10, 2006.Interpretive Summary: Zinc plays important roles in maintaining normal function of the prostate and in tumor development of prostate epithelia. Evidence has shown that prostate malignant epithelial cells (prostatic fluid secretion cells) contain much less cellular zinc than the surrounding normal epithelial cells. We characterized the zinc metabolic features of two human prostate epithelial cell lines (normal and cancerous cells which shared the same genetic background). We found that the cancerous prostate epithelia (RWPE2) accumulate 39% less cell-associated zinc than its normal counterpart (RWPE1) when they were incubated in culture media containing 75 'M ZnSO4 for 2 days. The results were further confirmed by 65Zn accumulation assay which indicated that RWPE2 accumulated 48% less isotope than RWPE1 over a period of 60 minutes. The low capacity for cellular zinc accumulation in RWPE2 was due to the reduced zinc uptake activity. The mRNA expression of two zinc uptake genes, ZIP1 and ZIP3, in RWPE1 and RWPE2 was comparable. However, the protein expression of ZIP1 was down-regulated in RWPE2. Part of ZIP3 was detected in a lysosomal compartment (a place in the cell where unused materials are being degraded or stored) of RWPE2 whereas it was not detected in the lysosomal compartment of in RWPE1. It is hypothesized here that the down-regulation of ZIP1 expression and intracellular redistribution of ZIP3 may cause low capacity for zinc accumulation in RWPE2. Finally, over-expression of ZIP1 in RWPE2 resulted in an elevation of intracellular zinc and suppression of cell growth through programmed cell death.
                                Technical Abstract: Zinc plays important roles in maintaining normal function of the prostate and in tumorigenesis of prostate epithelia. Evidence has shown that prostate malignant epithelial cells contain much less cellular zinc than the surrounding normal epithelial cells. We characterized the zinc homeostatic features of two human prostate epithelial cell lines (non-tumorigenic and tumorigenic cells which shared the same genetic background). We found that the tumorigenic prostate epithelia (RWPE2) accumulate 39% less cell-associated zinc than its non-tumorigenic counterpart (RWPE1) when they were incubated in culture media containing 75 'M ZnSO4 for 2 days. The results were further confirmed by 65Zn accumulation assay which indicated that RWPE2 accumulated 48% less isotope than RWPE1 over a period of 60 minutes. The low capacity for cellular zinc accumulation in RWPE2 was due to the reduced zinc uptake activity. The mRNA expression of two zinc uptake genes, ZIP1 and ZIP3, in RWPE1 and RWPE2 was comparable. However, the protein expression of ZIP1 was down-regulated in RWPE2. Part of ZIP3 was detected in a lysosomal compartment of RWPE2 whereas it was not detected in the lysosomal compartment of in RWPE1. It is hypothesized here that the down-regulation of ZIP1 expression and intracellular redistribution of ZIP3 may cause low capacity for zinc accumulation in RWPE2.  Finally, over-expression of ZIP1 in RWPE2 resulted in an elevation of intracellular zinc and suppression of cell growth through apoptosis.


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