Down-regulation of transforming growth factor beta receptor type III in hepatocellular carcinoma is not directly associated with genetic alterations or loss of heterozygosity.
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.
Bae
Hyun Jin
HJ
Department of Pathology, Microdissection Genomics Research Center, College of Medicine, The Catholic University of Korea, Seoul 137-701, Korea.
Eun
Jung Woo
JW
Noh
Ji Heon
JH
Kim
Jeong Kyu
JK
Jung
Kwang Hwa
KH
Xie
Hong Jian
HJ
Park
Won Sang
WS
Lee
Jung Young
JY
Nam
Suk Woo
SW
D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000502:physiology
D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan