Abstract |
The X protein of the hepatitis B virus transactivates various cellular and viral promoters and enhancers. In this study, wild-type and mutants of the X gene, including the point mutations at codons 130 (AAG-->ATG, lysin--> methionine) and 131 (GTC-->ATC, valine--> isoleucine), commonly found in patients with human hepatocellular carcinoma (HCC), or deletions encompassing the same region, were cloned and inserted into expression vectors. Functional analysis of the mutants of the X gene was performed on the long terminal repeat of the Rous sarcoma virus in a transient transfection assay. A transactivating function was observed in the vector containing point mutations at codons 130 and 131 at the same level as that of wild-type X gene. Two constructs, each containing a different type of 8-nucleotide deletion mutant ( codons 128-130 or 130-132,) dramatically lost their transactivating function. These findings suggest that the transactivating function is not necessarily associated with the development of HCC, and that not only transactivation by the X gene but also the mutation-enhanced oncogenic potential of the gene products could contribute to hepatocarcinogenesis.
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Authors | Masami Minemura, Yukihiro Shimizu, Katsuharu Hirano, Yasuhiro Nakayama, Yoshiharu Tokimitsu, Kazuto Tajiri, Kazuki Yamada, Feng Xue, Terumi Takahara, Akiharu Watanabe, Toshiro Sugiyama |
Journal | Oncology reports
(Oncol Rep)
Vol. 14
Issue 2
Pg. 495-9
(Aug 2005)
ISSN: 1021-335X [Print] Greece |
PMID | 16012736
(Publication Type: Journal Article)
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Chemical References |
- Trans-Activators
- Viral Regulatory and Accessory Proteins
- hepatitis B virus X protein
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Topics |
- Animals
- Avian Sarcoma Viruses
(genetics)
- Base Sequence
- Carcinoma, Hepatocellular
(genetics, pathology)
- Cell Line, Tumor
- Cell-Free System
- Genetic Vectors
(genetics)
- Humans
- Molecular Sequence Data
- Mutation
- Protein Biosynthesis
(genetics)
- Rabbits
- Reticulocytes
(metabolism)
- Sequence Homology, Nucleic Acid
- Trans-Activators
(genetics)
- Transcription, Genetic
(genetics)
- Transcriptional Activation
(genetics)
- Transfection
- Viral Regulatory and Accessory Proteins
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