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• W2977772732 abstract "3273 The genetic/molecular basis of the development and progression of prostate cancer is largely unidentified. The most consistent and persistent distinguishing characteristic of malignant prostate is the inability of the malignant epithelial cells to accumulate zinc. A key factor in the malignant process is the mechanism that results in this inability of the neoplastic prostate cell to accumulate zinc. Recent studies identified ZIP1 (SLC39A1) as an important zinc transporter involved in the uptake and accumulation of zinc by prostate cells: up-regulation of hZIP1 in prostate cells increases zinc accumulation, which inhibits cell growth and increases net citrate production; down-regulation of hZIP1 decreases zinc accumulation in prostate cells 1-5. The down-regulation of hZIP1 transporter expression appears to be an essential factor in the development and progression of malignant prostate cells. We have shown that hZIP1 gene expression, which is expressed in normal peripheral zone glandular epithelium (the zone where prostate cancer occurs most often), is down-regulated in adenocarcinomatous glands. Correspondingly, the zinc level is depleted in the malignant glands. Down-regulation of hZIP1 and consecutive zinc depletion is a critical early event in the development of prostate malignancy. The intracellular zinc concentration in situ was measured using the zinc indicator dye Newport Green DCF (Molecular Probes, Eugene, OR). In our studies, three steroid hormones-testosterone, beta-estrodial and prolactin-at varying concentrations (ranging from 1ng/ml to 10,000ng /ml and combinations) were tested on five different cell lines, each exhibiting different characteristics with regards to their dependency on various hormones. The five cell lines utilized were: 1) LnCAP, PC3, RWPE-1, RWPE-2 and CA-HPV-10. After exposure to the three different hormones separately or in combination overnight or for two hours, the zinc uptake of the prostate cells was assayed by utilizing zinc indicators. The intracellular levels of zinc were measured by an Elisa based reader and by fluorescent microscopic visualization. The hZIP1, hZIP2, hZIP4 genes expression were analyzed by performing RT-PCR using RNA extracted from hormone-treated cells as a template. We have determined that: i) high concentrations of testosterone drastically decrease the zinc uptake, ii) a combination of low testosterone and relatively high estrogen and high prolactin increases zinc uptake in prostate cell lines and the same combination gives a two fold higher expression of both hZIP1 and hZIP2. Implications of a potential therapy or prevention for prostate cancer utilizing a zinc supplement plus a combination of hormones will be presented." @default.
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• W2977772732 date "2006-04-15" @default.
• W2977772732 modified "2023-09-26" @default.
• W2977772732 title "Estrogen and prolactin upregulate zinc transports and zinc uptake in the prostate cancer cell lines" @default.
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