Cancer Cell Biology
Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines†
Article first published online: 11 NOV 2004
Copyright © 2004 Wiley-Liss, Inc.
International Journal of Cancer
Volume 114, Issue 2, pages 209–218, 20 March 2005
How to Cite
Fujii, C., Nakamoto, Y., Lu, P., Tsuneyama, K., Popivanova, B. K., Kaneko, S. and Mukaida, N. (2005), Aberrant expression of serine/threonine kinase Pim-3 in hepatocellular carcinoma development and its role in the proliferation of human hepatoma cell lines. Int. J. Cancer, 114: 209–218. doi: 10.1002/ijc.20719
DNA Data Bank of Japan Accession Number AB114795.
- Issue published online: 18 JAN 2005
- Article first published online: 11 NOV 2004
- Manuscript Accepted: 1 SEP 2004
- Manuscript Received: 14 MAY 2004
- protein serine-threonine kinases;
- pre-malignant lesions;
- hepatocellular carcinoma;
- RNA interference;
Most cases of human hepatocellular carcinoma develop after persistent chronic infection with human hepatitis B virus or hepatitis C virus, and host responses are presumed to have major roles in this process. To recapitulate this process, we have developed the mouse model of hepatocellular carcinoma using hepatitis B virus surface antigen transgenic mice. To identify the genes associated with hepatocarcinogenesis in this model, we compared the gene expression patterns between pre-malignant lesions surrounded by hepatocellular carcinoma tissues and control liver tissues by using a fluorescent differential display analysis. Among the genes that were expressed differentially in the pre-malignant lesions, we focused on Pim-3, a member of a proto-oncogene Pim family, because its contribution to hepatocarcinogenesis remains unknown. Moreover, the unavailability of the nucleotide sequence of full-length human Pim-3 cDNA prompted us to clone it from the cDNA library constructed from a human hepatoma cell line, HepG2. The obtained 2,392 bp human Pim-3 cDNA encodes a predicted open reading frame consisting of 326 amino acids. Pim-3 mRNA was selectively expressed in human hepatoma cell lines, but not in normal liver tissues. Moreover, Pim-3 protein was detected in human hepatocellular carcinoma tissues and cell lines but not in normal hepatocytes. Furthermore, cell proliferation was attenuated and apoptosis was enhanced in human hepatoma cell lines by the ablation of Pim-3 gene with RNA interference. These observations suggest that aberrantly expressed Pim-3 can cause autonomous cell proliferation or prevent apoptosis in hepatoma cell lines. © 2004 Wiley-Liss, Inc.