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Actin and Vimentin proteins with N-terminal deletion detected in tumor-bearing rat livers induced by intraportal-vein injection of Ha-ras-transfected rat liver cells
Article first published online: 18 DEC 2008
Copyright © 2008 Wiley-Liss, Inc.
International Journal of Cancer
Volume 124, Issue 11, pages 2512–2519, 1 June 2009
How to Cite
Nakamura, Y., Kominami, A., Tsujimoto, Y., Nakayama, Y., Kitahashi, T., Yoshimoto, S., Kubo, A., Watanabe, S., Kageyama, M., Yokoyama, M., Kido, Y., Kobayashi, Y., Kuwahata, M., Chang, C.-C., Upham, B. L., Trosko, J. E., Park, E. Y. and Sato, K. (2009), Actin and Vimentin proteins with N-terminal deletion detected in tumor-bearing rat livers induced by intraportal-vein injection of Ha-ras-transfected rat liver cells. Int. J. Cancer, 124: 2512–2519. doi: 10.1002/ijc.24229
- Issue published online: 25 MAR 2009
- Article first published online: 18 DEC 2008
- Accepted manuscript online: 18 DEC 2008 12:00AM EST
- Manuscript Accepted: 21 NOV 2008
- Manuscript Received: 1 AUG 2008
- Sumitomo Foundation
- NIEHS. Grant Number: R01 ES013268-01A2
- gap junctional intercellular communication;
- ras oncogene;
The introduction of the tumorigenic v-Ha-ras oncogene-transformed rat liver epithelial cells (WBras), which is deficient in gap junctional intercellular communication (GJIC), into F344 rats, induces significant formation of hepatocellular tumors. GJIC plays a major role in maintaining tissue homeostasis. Using this in vivo tumor model system, we used 2-dimensional electrophoresis with isoelectric focusing in the first dimension and SDS-PAGE in the second dimension to globally identify proteins that are uniquely expressed in the livers of WBras-treated rats as compared to the sham control. Immunoblotting was used to identify Ras and Connexin43, which were the positive and negative marker proteins, respectively, of the introduced WBras cells. As predicted, immunoblotting indicated that the whole liver of tumor-bearing animals exhibited a decreased level of Connexin43 and an increased level of Ras. Connexin43 and GJIC were expressed and functional in normal liver, but not in the tumor. In addition to these 2 markers, an additional 4 proteins exhibited decreased levels and 2 proteins exhibited increased levels in the livers of tumor-bearing animals. N-Terminal sequencing analysis was used to identify these proteins, which were glucose-regulated protein 78, 2 isoforms of heat shock protein 60, and the β-chain of ATP synthase for the down regulated proteins, and β-Actin with a 46 amino acid deletion from its N-terminus and Vimentin with a 71 amino acid deletion from its N-terminus for the up regulated proteins. These data offer potentially new markers of liver tumorigenicity, particularly, Vimentin. © 2008 Wiley-Liss, Inc.