This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Deng, J. Articles by Hung, M.-C. Search for Related Content PubMed PubMed Citation Articles by Deng, J. Articles by Hung, M.-C.

The NH₂-Terminal and Conserved Region 2 Domains of Adenovirus E1A Mediate Two Distinct Mechanisms of Tumor Suppression¹

Department of Molecular and Cellular Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030

Adenovirus E1A has been shown to suppress tumor growth and induce apoptosis in response to stress. To determine the mechanisms and regions of E1A that mediate these functions, we characterized stable transfectants of various E1A mutants in murine melanoma cells both in vitro and in vivo. Three E1A-mutant constructs were used in this study, those having a single deletion at either the NH₂-terminal (dl1101) or conserved region 2 (CR2) domain (dl1108), or double deletions at both domains (dl0108). The in vitro study showed that the CR2 domain is required for E1A-mediated apoptosis, whereas the NH₂-terminal domain is dispensable. The in vivo study showed that dl1101 and dl1108 were still able to suppress tumor growth, whereas dl0108 lost tumor-suppressive activity. By in situ immunohistostaining, we found that factor VIII, a marker for angiogenesis, was greatly suppressed in dl1108 transfectants that are resistant to apoptosis. Thus, inhibition of angiogenesis is involved in the NH₂-terminal domain of E1A. In conclusion, we suggest that the NH₂-terminal and CR2 domain of E1A mediate two distinct mechanisms of tumor suppression.

This article has been cited by other articles:

				P. Pelka, J. N. G. Ablack, G. J. Fonseca, A. F. Yousef, and J. S. Mymryk Intrinsic Structural Disorder in Adenovirus E1A: a Viral Molecular Hub Linking Multiple Diverse Processes J. Virol., August 1, 2008; 82(15): 7252 - 7263. [Full Text] [PDF]

				H. Itamochi, J. Kigawa, Y. Kanamori, T. Oishi, C. Bartholomeusz, R. Nahta, F. J. Esteva, N. Sneige, N. Terakawa, and N. T. Ueno Adenovirus type 5 E1A gene therapy for ovarian clear cell carcinoma: a potential treatment strategy Mol. Cancer Ther., January 1, 2007; 6(1): 227 - 235. [Abstract] [Full Text] [PDF]

				Z. Zhou, H. Guan, and E. S. Kleinerman E1A Specifically Enhances Sensitivity to Topoisomerase II{alpha} Targeting Anticancer Drug by Up-Regulating the Promoter Activity Mol. Cancer Res., May 1, 2005; 3(5): 271 - 275. [Abstract] [Full Text] [PDF]

				S. M. Frisch E1A as a Tumor Suppressor Gene: Commentary re S. Madhusudan et al. A Multicenter Phase I Gene Therapy Clinical Trial Involving Intraperitoneal Administration of E1A-Lipid Complex in Patients with Recurrent Epithelial Ovarian Cancer Overexpressing HER-2/neu Oncogene. Clin Cancer Res 2004;10:2905-2907. Clin. Cancer Res., May 1, 2004; 10(9): 2905 - 2907. [Full Text] [PDF]

				T. Kawashima, S. Kagawa, N. Kobayashi, Y. Shirakiya, T. Umeoka, F. Teraishi, M. Taki, S. Kyo, N. Tanaka, and T. Fujiwara Telomerase-Specific Replication-Selective Virotherapy for Human Cancer Clin. Cancer Res., January 1, 2004; 10(1): 285 - 292. [Abstract] [Full Text] [PDF]

				B. D. Yu, M. Becker-Hapak, E. L. Snyder, M. Vooijs, C. Denicourt, and S. F. Dowdy Distinct and nonoverlapping roles for pRB and cyclin D:cyclin-dependent kinases 4/6 activity in melanocyte survival PNAS, December 9, 2003; 100(25): 14881 - 14886. [Abstract] [Full Text] [PDF]