Human Selenium Binding Protein Mediates Selenium Growth Inhibition of Prostate Cancer Cells
Posted on: Tuesday, 21 December 2004, 03:00 CST
Prostate Cancer
Human Selenium Binding Protein Mediates Selenium Growth Inhibition of Prostate Cancer Cells. C. Gao, Y. Wang, C. Chen, L. Feldman, and A. J. Sytkowski. Laboratory for Cell and Molecular Biology, Division of Hematology and Oncology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Low levels of dietary selenium are associated with increased cancer risk, and selenium compounds exhibit a chemopreventive effect for malignancies of several organs, including the prostate. Recently, treatment of LNCaP human prostate cancer cells with selenomethionine was reported to cause G1 arrest and 80% reduction in the S phase whereas no such effect was found with another prostate cancer line, PC-3 (1). Interestingly, we had shown previously that human selenium-binding protein hSP56, the human homologue of a rodent protein implicated in chemoresistance, is highly expressed in androgen-sensitive LNCaP cells but not in androgen-insensitive PC-3 cells. This expression in LNCaP cells is reversibly downregulated by androgen in vitro (2). Together, these data suggest that selenium modulation of prostate cancer cell growth may be mediated, at least in part, by hSP56. To test this hypothesis, we downregulated hSP56 in LNCaP cells with siRNA and stably overexpressed it in PC-3 cells. The cells were treated with selenomethionine. Growth of selenium-treated LNCaP cells with low hSP56 was increased significantly over that of wild type LNCaP cells, indicating that selenium's antiproliferative effect was diminished as hSP56 expression was reduced. Conversely, the growth of PC-3 cells with upregulated hSP56 was markedly inhibited by selenium treatment. Growth of these PC-3/hSP56 cells in soft agar was also markedly reduced. These data strongly suggest that hSP56 mediates part or all of selenium's antiproliferative action on these prostate cancer cells. hSP56 may be a novel tumor suppressor. [Supported by American Institute for Cancer Research grant 02A118- REN.]
1. Venkateswaran, V., Klotz, L. H. & Fleshner, N. E. (2002) Selenium modulation of cell proliferation and cell cycle biomarkers in human prostate carcinoma cell lines. Cancer Res. 62: 2540-2545.
2. Yang, M. & Sytkowski, A. J. (1998) Differential expression and androgen regulation of the human selenium-binding protein gene hSP56 in prostate cancer cells. Cancer Res. 58: 3150-3153.
Copyright American Institute of Nutrition Dec 2004
Source: Journal of Nutrition, The
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