Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate glands contain heavy metals such as zinc and cadmium, and epidemiological studies showed that both metals were associated with prostate cancer development. To understand the heavy metal metabolism in prostate glands, we investigated the regulation of metallothionein (MT), metal-responsive promoter element-binding transcription factor (MTF) and zinc transporter (ZnT) in human prostate cells and tissues. Growth of human prostate cancer cells, LNCaP and PC-3 cells, was suppressed by zinc or cadmium treatment in a dose-dependent manner. LNCaP cells expressed MT-1A, 1X and 2A mRNA, and PC-3 cells expressed MT-1X and 2A mRNA. Zinc or cadmium treatment up-regulated MTs, MTF-1 and ZnT-1 gene expression levels in both cell lines. In PC-3 cells, ZnT-1 protein was detected, and was up-regulated by the metal treatment. Human prostate cancer tissues expressed significantly lower levels of ZnT-1 gene in comparison with hyperplastic tissues. We demonstrated the ZnT-1 expression in human prostate for the first time. The present study showed that heavy metal-metabolizing proteins were involved in human prostate homeostasis, and that the metal metabolizing system might be different in malignant tissues.
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PMID:Regulation of metallothionein and zinc transporter expression in human prostate cancer cells and tissues. 1456 74

The human prostate gland has low basal expression of the metallothionein-1 and -2 proteins. In prostate cancer, MT-1/2 protein expression is variable and correlates directly with the increasing Gleason score of the tumor. The goal of the present study was to determine if the RWPE-1 cell line is a good model to elucidate the mechanisms underlying the alterations in MT-1/2 expression that occur during the development of prostate cancer. It was shown that the RWPE-1 cell line and in situ prostate tissue have identical expression profiles of MT-1 and MT-2 isoform-specific mRNAs (MT-1E, MT-1X and MT-2A) and similar levels of MT-1/2 protein. It was also shown that the RWPE-1 cells respond to Zn(+2) and Cd(+2) exposure by induction of the basally expressed MT mRNAs and the accumulation of high levels MT-1/2 protein (in excess of 10% of total protein). It was also shown that additional MT-1 mRNAs were expressed when the cells were exposed to either metal; MT-1A, MT-1F, MT-G and MT-1H for Cd(+2)-exposed cells; and, MT-1F, MT-G and MT-1H for Zn(+2)-exposed cells. The results suggest that RWPE-1 cells may be a valuable system to define the interplay between Zn(+2) concentration, Cd(+2) exposure and MT in normal and malignant prostate epithelial cells.
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PMID:Basal and metal-induced expression of metallothionein isoform 1 and 2 genes in the RWPE-1 human prostate epithelial cell line. 1759 Aug 60

Tumor hypoxia is a common feature of several cancers, including prostate cancer, and is associated with tumor progression, acquisition of anti-apoptotic potential and therapeutic resistance. We explored hypoxia-inducible genes and examined the effect of knockdown of a target molecule with small interference RNA (siRNA) on the proliferation of human prostate cancer cells. Human prostate cancer cell lines (LNCaP and PC-3) were cultured in normoxia (21% O2) or hypoxia (0.5% O2). Hypoxia-inducible genes were identified by cDNA microarray analysis. Metallothionein (MT) expression was assessed by real-time RT-PCR, Western blot analysis and immunohistochemical staining. siRNA was transfected to knock down MT expression, and the cell cycle and apoptosis were evaluated by flow cytometry analysis. In cDNA microarray analysis, 22 genes (including MT) were up-regulated under hypoxia. MT-1X and MT-2A were up-regulated in real-time RT-PCR. In particular, MT-2A was increased 3-fold in LNCaP and 8-fold in PC-3. The siRNA-MT-2A treatment resulted in a 20% inhibition of cell growth and induced apoptosis in both LNCaP and PC-3. In human prostate tissue, intense staining of MT was observed in cancer cells and residual cancer cells after androgen ablation therapy, while normal tissue was only stained in patches. In conclusion, MT was up-regulated under hypoxia in prostate cancer cells and overexpressed in prostate cancer tissue and residual cancer cells after androgen ablation therapy. As down-regulation of MT by siRNA inhibited cell growth and induced cell death, MT may be a new molecular target for the treatment of human prostate cancer.
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PMID:Metallothionein is up-regulated under hypoxia and promotes the survival of human prostate cancer cells. 1791 65