Dermatopontin is expressed in human liver and is downregulated in hepatocellular carcinoma
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Dermatopontin (DPT) was recently found as a downstream target of vitamin D receptor, which is a key molecule in the 1,25-dihydroxy-vitamin D3 anti-hepatoma proliferation pathway. MCTx-1 from Millepora, a homolog of DPT, is identified as a cytotoxin towards leukemia cells. The aim of this study was to analyze DPT expression in hepatocellular carcinoma (HCC) based on the analysis for DPT gene in normal tissues in order to estimate its function in the progression of HCC. DPT mRNA expression was analyzed in normal tissues and HCC cell lines by RT-PCR, and in HCC tissue by RT-PCR and real-time PCR. Its protein was examined in HCC tissues by Western blot and immunohistochemistry assays. Meanwhile, transforming growth factor-β1 (TGF-β1) that is closely associated with HCC and DPT was observed by immunohistochemistry in HCC tissues. The results showed that DPT mRNA was strongly expressed in human fetal and adult liver, kidney, and spleen, weakly in ovary and heart, and absent in other tissues and HCC cell lines examined. Its mRNA was significantly downregulated in HCC tissues, while its protein was weakly expressed in tumor compared with non-tumor. DPT is located mainly in the cytoplasm of several cell types in the liver; it has been identified also in the extra-cellular matrix of the skin. TGF-β1 was observed in extensive tumor tissue of HCC. This fact suggests that DPT can play various roles in different tissues and might be a molecule related to carcinogenesis and the progression of HCC via possible interaction with TGF-β1 and other potential mechanisms.
Key wordsliver hepatocellular carcinoma dermatopontin transforming growth factor-β1
hepatic stellate cells
sinusoidal endothelial cells
transforming growth factor-β1
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