E1a is an exogenous in vivo tumour suppressor

Publication date: 28 July 2017
Source:Cancer Letters, Volume 399
Author(s): Francisco J. Cimas, Juan L. Callejas-Valera, Dolores C. García-Olmo, Javier Hernández-Losa, Pedro Melgar-Rojas, María J. Ruiz-Hidalgo, Raquel Pascual-Serra, Marta Ortega-Muelas, Olga Roche, Pilar Marcos, Elena Garcia-Gil, Diego M. Fernandez-Aroca, Santiago Ramón y Cajal, J. Silvio Gutkind, Ricardo Sanchez-Prieto
The E1a gene from adenovirus has become a major tool in cancer research. Since the discovery of E1a, it has been proposed to be an oncogene, becoming a key element in the model of cooperation between oncogenes. However, E1a's in vivo behaviour is consistent with a tumour suppressor gene, due to the block/delay observed in different xenograft models. To clarify this interesting controversy, we have evaluated the effect of the E1a 13s isoform from adenovirus 5 in vivo. Initially, a conventional xenograft approach was performed using previously unreported HCT116 and B16-F10 cells, showing a clear anti-tumour effect regardless of the mouse's immunological background (immunosuppressed/immunocompetent). Next, we engineered a transgenic mouse model in which inducible E1a 13s expression was under the control of cytokeratin 5 to avoid side effects during embryonic development. Our results show that E1a is able to block chemical skin carcinogenesis, showing an anti-tumour effect. The present report demonstrates the in vivo anti-tumour effect of E1a, showing that the in vitro oncogenic role of E1a cannot be extrapolated in vivo, supporting its future use in gene therapy approaches.



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