2024-03-28T18:05:22Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/2212202022-06-24T11:47:09Zcom_10261_22com_10261_1col_10261_275
http://hdl.handle.net/10261/221220
10.1016/j.canlet.2017.04.010
402132
E1a is an exogenous in vivo tumour suppressor
Elsevier
2017
artículo
Cimas, Francisco J.
Callejas-Valera, Juan L.
García-Olmo, Dolores C.
Hernández-Losa, Javier
Melgar-Rojas, Pedro
Ruiz-Hidalgo, María J.
Pascual-Serra, Raquel
Ortega-Muelas, Marta
Roche, Olga
Marcos, Pilar
García-Gil, Elena
Fernández-Aroca, Diego M.
Ramón y Cajal, Santiago
Gutkind, J. Silvio
Sánchez-Prieto, Ricardo
E1a
Tumour suppressor
Oncogene
Transgenic mouse
Skin carcinogenesis
Gene therapy
2017-07-28
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.
Fundación Leticia Castillejo
Ministerio de Economía y Competitividad (España)
Junta de Comunidades de Castilla-La Mancha
Cancer Letters
2017
399
74
81