Cloning and characterization of a novel gene, DRH1, down-regulated in advanced human hepatocellular carcinoma.
2001; National Institutes of Health; Volume: 7; Issue: 2 Linguagem: Inglês
Autores
Yoshiya Yamamoto, Michiie Sakamoto, Gen Fujii, Kengo Kanetaka, Masahiro Asaka, Setsuo Hirohashi,
Tópico(s)Cancer-related Molecular Pathways
ResumoFew genes related to carcinogenesis and progression of hepatocellular carcinoma (HCC) have been identified to date. In the present study, we report the cloning and characterization of a novel gene, DRH1, which is frequently down-regulated in HCC. The full-length DRH1 clone contains an open reading frame of 1257 nucleotides encoding 419 amino acids. The deduced DRH1 protein shows 41% identity to VDUP1, expression of which is rapidly induced by 1,25-dihydroxyvitamin D3. The DRH1 gene was localized to chromosome 15, and DRH1 protein was mainly observed in the cytoplasm of transiently transfected cells. Real-time quantitative reverse transcription-PCR analysis showed that the expression level of DRH1 was reduced in 29 of 35 (83%) HCCs compared with corresponding noncancerous liver tissue. The average (mean +/- SE) ratio of DRH1 expression level in tumor to corresponding noncancerous tissue was significantly different between well, moderately, and poorly differentiated HCCs (1.15 +/- 0.23, 0.69 +/- 0.10, and 0.19 +/- 0.04, respectively) and between HCCs without and with vascular invasion (0.94 +/- 0.16 and 0.46 +/- 0.07, respectively). These results indicate that the down-regulation of DRH1 occurs not at an early stage but rather at a late stage of HCC progression. Although the function of DRH1 protein is still unknown, our findings suggest that DRH1 is related to the progression of HCC and may provide a new prognostic factor.
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