| Autor: |
Miyaki, Michiko, Sato, Chieko, Sakai, Kimiyo, Konishi, Motoko, Tanaka, Kiyoko, Muraoka, Masatoshi, Kikuchi-Yanoshita, Rei, Nadaoka, Yoko, Kanda, Hiroaki, Kitagawa, Tomoyuki |
| Zdroj: |
International Journal of Cancer; 15 February 2000, Vol. 85 Issue: 4 p518-522, 5p |
| Abstrakt: |
We have previously observed that all human hepatocellular carcinomas (HCCs) from HBV carriers examined had the integrated X region. In this study, HBV DNA was isolated from an integration site in one HCC that had a single, very small integrated viral DNA including the X region, but it had no expression of X gene as poly(A)RNA. It was found that HBV DNA was present between alphoid repetitive sequences, and it included Enhancer and X regions, encompassing the adr sequence from 910 to 1811. Nucleotides for 8 amino acids at the 3 end, a stop codon of X gene and a poly(A) signal downstream of X gene were lost by integration, and nucleotides for 7 amino acids and a stop codon were substituted by a connected alphoid sequence. When this cloned HBV DNA was transfected with an expression vector to an immortalized mouse liver epithelial cell line, MLE-10, malignant transformation occurred. Transformants having expressed poly(A)RNA of the X gene showed anchorage-independent growth in soft agar and tumor formation in the subcutis of nude mice. The mRNA level of EGFR was found to be remarkably enhanced in X-transformed cells, in contrast with the absence of this mRNA in parental and ras-transformed MLE-10. Our data provide evidence that the Enhancer-X region alone is the key contributor to the malignant change of pre-malignant liver cells in HBV carriers through activation of some specific genes, such as EGFR. Int. J. Cancer 85:518522, 2000. © 2000 Wiley-Liss, Inc. |
| Databáze: |
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