Abstract
BackgroundZinc plays important roles in maintaining normal function of the prostate and in development of prostate malignancy. It has been demonstrated that prostate malignant epithelial cells contain much less cellular zinc than the surrounding normal epithelial cells. However, the pathway(s) which leads to lower zinc accumulation in malignant prostate epithelial cells is poorly understood. In this study, the zinc homeostatic features of two human prostate epithelial cell lines (non-tumorigenic, RWPE1, and tumorigenic, RWPE2) were investigated. Effects of over-expression of ZIP1 in RWPE2 on cell proliferation and apoptosis were also studied.ResultsRWPE2 accumulated less intracellular zinc than RWPE1 due to the decreased zinc uptake activity. The mRNA expression of ZIP1 and ZIP3 in RWPE1 and RWPE2 was comparable. However, the protein expression of ZIP1 in RWPE2 was lower than that in RWPE1. ZIP3 was detected in a lysosomal compartment of RWPE2 while no ZIP3 was detected in the same compartment of RWPE1. Over-expression of ZIP1 in RWPE2 resulted in an elevation of intracellular zinc concentration and suppression of cell growth of RWPE2 due to the increased apoptosis.ConclusionThese findings suggest that tumorigenic prostate epithelial cells accumulated less intracellular zinc than non-tumorigenic prostate epithelial cells. The reduction in capacity for accumulation of intracellular zinc in tumorigenic prostate epithelial cells may be caused by the decrease in the ZIP1 protein expression and the intracellular redistribution of ZIP3 in RWPE2. RWPE1 and RWPE2 are excellent cellular models to study the association of intracellular zinc levels with prostate cancer progression.
Highlights
Zinc plays important roles in maintaining normal function of the prostate and in development of prostate malignancy
We found that the capacity for zinc accumulation was decreased in RWPE2 because of the aberrant protein expression and cellular localization of zinc uptake proteins, ZIP1 and ZIP3
In order to elucidate the molecular basis underlying this clinical finding, we studied the zinc homeostatic features of two existing prostate epithelial cell lines, RWPE1, a non-tumorigenic prostate epithelial cell line, and RWPE2, its tumorigenic counterpart
Summary
Zinc plays important roles in maintaining normal function of the prostate and in development of prostate malignancy. The glandular epithelial cells in the dorsolateral lobe of the prostate accumulate the highest levels of intracellular zinc [3,7] This is the area where most prostate cancers (page number not for citation purposes). Cancer Cell International 2006, 6:10 http://www.cancerci.com/content/6/1/10 occur This observation strongly suggests that zinc has an important role in prostate cancer development and/or progression. Studies have indicated that the intracellular zinc levels in malignant prostate epithelial cells are dramatically decreased [8,9]. This contrasts with benign prostatic hyperplasia in which the epithelial cells accumulate normal or higher levels of zinc [8,9]. Zinc is an important factor in prostate biology and pathology, the exact roles of zinc and its homeostatic regulation in the normal and malignant prostate glands are not understood
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