Down-regulation of transforming growth factor beta receptor type III in hepatocellular carcinoma is not directly associated with genetic alterations or loss of heterozygosity

초록

The transforming growth factor receptor III (TGF beta RIII) 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 TGF beta RIII was reported to be decreased in a variety of human cancers. Functional assessment of TGF beta RIII was performed in many previously studied cancers but not in hepatocellular carcinoma. Therefore, in this study, we investigated the expression and genetic alterations of TGF beta RIII 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 TGF beta RHI in the tumor samples. To investigate whether genetic alterations mediated decreased expression of TGF beta RIII, 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 (T (C) under barC -> T (C) under barC, 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 TGF beta RIII is transcriptionally down-regulated in hepatocellular carcinoma. In addition, genetic alterations did not appear to be associated with the reduced expression level of TGF beta RIII. To clarify the role of TGF beta RIII in hepatocellular tumor development and progression, functional analysis is needed in future studies.

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