TY - JOUR
T1 - E1a is an exogenous in vivo tumour suppressor
AU - Cimas, Francisco J.
AU - Callejas-Valera, Juan L.
AU - García-Olmo, Dolores C.
AU - Hernández-Losa, Javier
AU - Melgar-Rojas, Pedro
AU - Ruiz-Hidalgo, María J.
AU - Pascual-Serra, Raquel
AU - Ortega-Muelas, Marta
AU - Roche, Olga
AU - Marcos, Pilar
AU - Garcia-Gil, Elena
AU - Fernandez-Aroca, Diego M.
AU - Ramón y Cajal, Santiago
AU - Gutkind, J. Silvio
AU - Sanchez-Prieto, Ricardo
PY - 2017/7/28
Y1 - 2017/7/28
N2 - © 2017 Elsevier B.V. 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.
AB - © 2017 Elsevier B.V. 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.
KW - E1a
KW - Gene therapy
KW - Oncogene
KW - Skin carcinogenesis
KW - Transgenic mouse
KW - Tumour suppressor
U2 - 10.1016/j.canlet.2017.04.010
DO - 10.1016/j.canlet.2017.04.010
M3 - Article
SN - 0304-3835
VL - 399
SP - 74
EP - 81
JO - Cancer Letters
JF - Cancer Letters
ER -