Bae Hyun Jin, Eun Jung Woo, Noh Ji Heon, Kim Jeong Kyu, Jung Kwang Hwa, Xie Hong Jian, Park Won Sang, Lee Jung Young, Nam Suk Woo
Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Oncol Rep. 2009 Sep;22(3):475-80.
The transforming growth factor receptor III (TGFbetaRIII) is the most abundant and essential TGF-beta binding protein that functions as a co-receptor with other receptors in TGF-beta signaling. In earlier studies, expression of TGFbetaRIII was reported to be decreased in a variety of human cancers. Functional assessment of TGFbetaRIII was performed in many previously studied cancers but not in hepatocellular carcinoma. Therefore, in this study, we investigated the expression and genetic alterations of TGFbetaRIII in hepatocellular carcinoma (HCC) by quantitative real-time PCR (qRT-PCR) and single-strand conformation polymorphism (SSCP) analysis. The qRT-PCR showed down-regulation of TGFbetaRIII in the tumor samples. To investigate whether genetic alterations mediated decreased expression of TGFbetaRIII, we performed mutation analysis of 67 human HCC tissues by SSCP and direct sequencing. We found five previously reported and one novel single nucleotide polymorphisms in exons 2, 3, 5, 13 and 14, but no mutations were detected. These polymorphisms were not associated with amino acid changes except for a base change found in exon 2 (TCC-->TTC, S15F). The loss of heterozygosity (LOH) analysis performed on 10 tumors and corresponding normal pairs, showed a low rate of LOH (2/10). The results of this study suggest that TGFbetaRIII is transcriptionally down-regulated in hepatocellular carcinoma. In addition, genetic alterations did not appear to be associated with the reduced expression level of TGFbetaRIII. To clarify the role of TGFbetaRIII in hepatocellular tumor development and progression, functional analysis is needed in future studies.
转化生长因子受体III（TGFβRIII）是最丰富且必不可少的TGF-β结合蛋白，在TGF-β信号传导中作为其他受体的共受体发挥作用。在早期研究中，据报道TGFβRIII在多种人类癌症中表达降低。此前在许多癌症中对TGFβRIII进行了功能评估，但未在肝细胞癌中进行。因此，在本研究中，我们通过定量实时PCR（qRT-PCR）和单链构象多态性（SSCP）分析，研究了TGFβRIII在肝细胞癌（HCC）中的表达及基因改变。qRT-PCR显示肿瘤样本中TGFβRIII表达下调。为研究基因改变是否介导了TGFβRIII表达降低，我们通过SSCP和直接测序对67例人类HCC组织进行了突变分析。我们在第2、3、5、13和14外显子中发现了5个先前报道的单核苷酸多态性和1个新的单核苷酸多态性，但未检测到突变。除第2外显子中发现的碱基变化（TCC→TTC，S15F）外，这些多态性与氨基酸变化无关。对10对肿瘤及相应正常组织进行的杂合性缺失（LOH）分析显示，LOH发生率较低（2/10）。本研究结果表明，TGFβRIII在肝细胞癌中存在转录下调。此外，基因改变似乎与TGFβRIII表达水平降低无关。为阐明TGFβRIII在肝细胞肿瘤发生和进展中的作用，未来研究需要进行功能分析。
