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Abrogation of p53-Induced Apoptosis by the Hepatitis B Virus X Gene

2025-03-20 细胞技术 加入收藏
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases w

Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases worldwide and has become a leading cause for cancer-related deaths in adults from Asia and sub-Saharan Africa (1 ). The DNA tumor virus hepatitis B virus (HBV) has been implicated to play a major causative role in the development of HCC in man (2 –4 ). The HBx gene, the smallest viral openreading frame that may be essential for the viral life cycle (5 ,6 ), largely contributes the oncogenecity of HBV. The selective retention and expression of the HBx gene during acute and chronic hepatitis as well as in a great majority of HCCs may constitute an important step during HCC development (7 ,8 ). The oncogenic potential of the HBx gene has been experimentally demonstrated in a transgenic mice model (9 ) and in cell culture systems (10 ,11 ). HBx alone can induce HCC in certain transgenic mice (9 ) or can increase susceptibility to chemical carcinogens (12 ) and accelerate c-myc-induced HCC (13 ). Consequently, as an oncoprotein, HBx has been reported to disregulate cell-cycle transition (14 ,15 ) to potentially target certain proteases and proteasome (16 –18 ), to interact with DNA repair factors (19 ,20 ), or to interact with the p53 tumor suppressor gene product (21 –24 ).

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