Effects of various steroid hormones on intracellular zinc uptake in prostate cancer cell lines

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Proc Amer Assoc Cancer Res, Volume 46, 2005 3204 The genetic/molecular basis of prostate cancer is unknown. 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. hZIP1 has been identified as an important zinc uptake transporter. We have shown that gene expression of hZIP1 is downregulated in malignant cells of prostate epithelia. This project we compared the effects of varying concentrations of steroid hormones on the uptake of zinc by different prostate tissue cell lines. 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, β-estrodial and prolactin- at varying concentrations, ranging in concentration from .125 nM to 1.22 x 10−4 nM, and were tested on three different cell lines, each exhibiting different characteristics with regards to their dependency on various hormones. The three cell lines were: 1.) LnCAP, (ATCC # CRL-1740), an androgen-dependent epithelial prostate carcinoma isolated from the supraclavicular lymph node, 2.) PC3, (ATCC # CRL-1435), an androgen dependent epithelial prostate andenocarcinoma isolated from bone marrow tissue, and 3.) RWPE, (ATCC # CRL-2221), prostate epithelial cell line from normal tissue and transformed with HPV-18. After exposure to the three different hormones overnight, 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 microscopic visualization. Our analyses show that there is a complex interplay between various hormones with regards to zinc uptake. Implication of a potential therapy or prevention for prostate cancer utilizing a zinc supplement plus a combination of hormones will be presented.

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