TY - JOUR
T1 - RXRα deletion and E6E7 oncogene expression are sufficient to induce cervical malignant lesions in vivo
AU - Ocadiz-Delgado, Rodolfo
AU - Castañeda-Saucedo, Eduardo
AU - Indra, Arup K.
AU - Hernandez-Pando, Rogelio
AU - Flores-Guizar, Pedro
AU - Cruz-Colin, Jose Luis
AU - Recillas-Targa, Felix
AU - Perez-Ishiwara, Guillermo
AU - Covarrubias, Luis
AU - Gariglio, Patricio
N1 - Funding Information:
We are grateful to Dr. Pierre Chambon and Dr. Daniel Metzger (IGBMC, CNRS, INSERM, Université Louis Pasteur, Illkirch-Cedex, Strasbourg, France) for the kind gift of their invaluable RXRα conditional mouse model and for helpful discussions. We would like to thank Dr. Diana Escalante-Alcalde (IBT-UNAM), Biol. Elizabeth Alvarez, Biol. Enrique García and Mr. Lauro Macías (CINVESTAV-IPN, Mexico) for technical support. This work was supported by CONACyT (Mexico) and ICGEB, CRP Programme, Trieste, Italy. PG was supported by a UICC Translational Cancer Research Fellowship, funded by Novartis (Switzerland). ECS was supported by the scholarship “Ligue Contre le Cancer comité de Bas-Rhin”.
PY - 2012/4/28
Y1 - 2012/4/28
N2 - Cervical cancer is the second leading cause of cancer deaths among women worldwide. High-Risk-Human Papillomaviruses (HR-HPVs) play an important etiologic role in the development of carcinoma of the uterine cervix. However, host factors are important in determining the outcome of genital HPV infection as most cervical precancerous lesions containing HR-HPVs do not progress to invasive carcinomas. Retinoids, acting through nuclear receptors (RARs, RXRs), play a crucial role in cervix development and homeostasis regulating growth and differentiation of a wide variety of cell types; indeed, they can inhibit cell proliferation, and induce cell differentiation or apoptotic cell death. Here we introduce a mouse model that develops spontaneously malignant cervical lesions allowing the study of the cooperative effect between HPV16E6E7 expression and the lack of RXRα in cervical cancer development. This model could be useful to study multistep carcinogenesis of uterine cervix tissue and might improve chemopreventive and chemotherapeutic strategies for this neoplasia.
AB - Cervical cancer is the second leading cause of cancer deaths among women worldwide. High-Risk-Human Papillomaviruses (HR-HPVs) play an important etiologic role in the development of carcinoma of the uterine cervix. However, host factors are important in determining the outcome of genital HPV infection as most cervical precancerous lesions containing HR-HPVs do not progress to invasive carcinomas. Retinoids, acting through nuclear receptors (RARs, RXRs), play a crucial role in cervix development and homeostasis regulating growth and differentiation of a wide variety of cell types; indeed, they can inhibit cell proliferation, and induce cell differentiation or apoptotic cell death. Here we introduce a mouse model that develops spontaneously malignant cervical lesions allowing the study of the cooperative effect between HPV16E6E7 expression and the lack of RXRα in cervical cancer development. This model could be useful to study multistep carcinogenesis of uterine cervix tissue and might improve chemopreventive and chemotherapeutic strategies for this neoplasia.
KW - Cervical cancer
KW - E6E7
KW - HPV
KW - Murine models
KW - Retinoid receptor
UR - http://www.scopus.com/inward/record.url?scp=84856606248&partnerID=8YFLogxK
U2 - 10.1016/j.canlet.2011.11.031
DO - 10.1016/j.canlet.2011.11.031
M3 - Artículo
SN - 0304-3835
VL - 317
SP - 226
EP - 236
JO - Cancer Letters
JF - Cancer Letters
IS - 2
ER -