Differential expression of metallothioneins (MTs) 1, 2, and 3 in response to zinc treatment in human prostate normal and malignant cells and tissues

Our results demonstrated a significant suppression of endogenous levels of MT1/2 in malignant PC-3 cells (95% reduction compared to the normal prostate cells) and in human adenocarcinoma tissues (73% MT1/2 negative). A moderate reduction of MT1/2 expression was observed in BPH. Zinc treatment remarkably induced MT1/2 expression in PC-3 and BPH cells, which was accordant with the restored cellular zinc level. MT 3, as a growth inhibitory factor, was detected and up-regulated by zinc mainly in BPH cells.This study provided evidence of the association of attenuated MT1/2 with prostate tumor progression, and the zinc induction of MT1/2 expression resulting in cellular zinc restoration. The results suggest the potential of MT1/2 as a candidate biomarker for prostate cancer and the utilization of zinc in prostate cancer prevention and treatment.Zinc is an essential element involved in many cellular functions and is required by approximately 300 enzymes for their biological activities [1]. In humans, deficiency of zinc might inhibit growth [2], but it is also closely related to increased risk of certain malignant tumors [3,4]. Normal prostate contains the highest zinc level, but a dramatic decrease of cellular zinc (60–70% loss) was found in malignant prostate cells [5]. We have demonstrated that zinc exposure induces apoptosis in malignant prostate PC-3 and benign hyperplasia prostate (BPH) cells, but not in normal prostate HPR-1 cells [6,7]. Despite few studies on the relationship of zinc accumulation and zinc-induced prostatic cell apoptosis [8-10], the mechanisms of the disturbance of zinc homeostasis and zinc restoration in relation to pathogenesis and malignancy of prostate tissues remain unclear.Cellular zinc homeostasis is modulated by many factors such as zinc transporters (ZnTs and ZIPs) and metallothioneins (MTs), which are involved in the aspects of zinc transport, trafficking, and signals [11]. Among these factors, MTs are of low molecular weight (~6 kd); mole