Department of Immunology, Sichuan University, Chengdu, Sichuan, 610041, China.
Biochemistry (Mosc). 2009 Sep;74(9):979-85. doi: 10.1134/s0006297909090053.
Dermatopontin (DPT) was recently found as a downstream target of vitamin D receptor, which is a key molecule in the 1,25-dihydroxy-vitamin D(3) 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-beta1 (TGF-beta1) 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 extracellular matrix of the skin. TGF-beta1 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-beta1 and other potential mechanisms.
真皮蛋白聚糖(DPT)最近被发现是维生素 D 受体的下游靶标,而维生素 D 受体是 1,25-二羟维生素 D(3)抗肝癌增殖途径中的关键分子。米氏软珊瑚中的 MCTx-1 是 DPT 的同源物,被鉴定为白血病细胞的细胞毒素。本研究旨在通过分析正常组织中的 DPT 基因,分析肝癌(HCC)中 DPT 的表达,以评估其在 HCC 进展中的功能。通过 RT-PCR 分析正常组织和 HCC 细胞系中的 DPT mRNA 表达,通过 RT-PCR 和实时 PCR 分析 HCC 组织中的 DPT mRNA 表达。通过 Western blot 和免疫组织化学检测 HCC 组织中的 DPT 蛋白。同时,通过免疫组织化学观察与 HCC 密切相关的转化生长因子-β1(TGF-β1)与 DPT 的关系。结果表明,DPT mRNA 在人胎肝、成人肝、肾和脾中强烈表达,在卵巢和心脏中弱表达,在其他组织和 HCC 细胞系中不表达。其 mRNA 在 HCC 组织中显著下调,而其蛋白在肿瘤中表达较弱。DPT 主要位于几种肝细胞的细胞质中;也在皮肤的细胞外基质中被鉴定出来。TGF-β1 在 HCC 的广泛肿瘤组织中被观察到。这一事实表明,DPT 可以在不同组织中发挥多种作用,并且可能通过与 TGF-β1 和其他潜在机制的相互作用,成为与肿瘤发生和 HCC 进展相关的分子。