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Adenovirus-mediated expression of truncated E2F-1 suppresses tumor growth in vitro and in vivo
Version of Record online: 19 AUG 2010
Copyright © 2010 American Cancer Society
Volume 116, Issue 18, pages 4420–4432, 15 September 2010
How to Cite
Gomez-Gutierrez, J. G., Garcia-Garcia, A., Hao, H., Rao, X.-M., Montes de Oca-Luna, R., Zhou, H. S. and McMasters, K. M. (2010), Adenovirus-mediated expression of truncated E2F-1 suppresses tumor growth in vitro and in vivo. Cancer, 116: 4420–4432. doi: 10.1002/cncr.25322
- Issue online: 3 SEP 2010
- Version of Record online: 19 AUG 2010
- Manuscript Accepted: 9 FEB 2010
- Manuscript Revised: 21 DEC 2009
- Manuscript Received: 16 SEP 2009
- in vivo
Adenovirus (Ad)-mediated E2F-1 gene transfer induces apoptosis in cancer cells in vitro and in vivo, but clinical application of E2F-1 in cancer gene therapy remains controversial because of the oncogenic potential of E2F-1. This barrier can be circumvented by using the truncated form of the E2F-1 gene (E2Ftr) (amino acids 1 through 375), which lacks the E2F-1 transactivation domain and cell cycle-promoting effects.
The authors constructed 3 adenoviral vectors that expressed E2Ftr under regulation of the tetracycline (Tet)-off system (AdTet-E2Ftr1, AdTet-E2Ftr2, and AdTet-E2Ftr3). These vectors were compared for E2Ftr expression and apoptosis induction in cancer cells and normal cells. E2Ftr antitumor activity in vivo also was assessed in a melanoma xenograft model.
One of the 3 vectors, AdTet-E2Ftr3, had the highest E2Ftr protein expression levels, which were correlated with the greatest induction of apoptosis and inhibition of cancer cell growth. E2Ftr induced apoptosis in a variety of cancer cell lines independent of p53 status with little cytotoxicity in normal cell lines. In a mouse melanoma xenograft model, AdTet-E2Ftr3 exhibited an approximately 80% decrease in tumor size compared with controls in vivo.
The current results indicated that AdTet-E2Ftr3 is a novel anticancer agent that has significant therapeutic activity in vitro and in vivo. Cancer 2010. © 2010 American Cancer Society.