title: RXRα deletion and E6E7 oncogene expression are sufficient to induce cervical malignant lesions in vivo.
abstract: 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.
authors.affiliation: Dept. of Genetics & Molecular Biology, Centro de Investigacion y de Estudios Avanzados del IPN (CINVESTAV-IPN). Av. IPN 2508, Col. San Pedro Zacatenco, 07360. Mexico, DF, Mexico.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Ocadiz-Delgado
authors.forename: Eduardo
authors.initials: E
authors.lastname: Castañeda-Saucedo
authors.forename: Arup K
authors.initials: AK
authors.lastname: Indra
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernandez-Pando
authors.forename: Pedro
authors.initials: P
authors.lastname: Flores-Guizar
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Cruz-Colin
authors.forename: Felix
authors.initials: F
authors.lastname: Recillas-Targa
authors.forename: Guillermo
authors.initials: G
authors.lastname: Perez-Ishiwara
authors.forename: Luis
authors.initials: L
authors.lastname: Covarrubias
authors.forename: Patricio
authors.initials: P
authors.lastname: Gariglio
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009856:Oncogene Proteins, Viral / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D047490:Retinoid X Receptor alpha / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; C068651:E6 protein, Human papillomavirus type 16; C489428:Myc protein, mouse; D009856:Oncogene Proteins, Viral; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D047490:Retinoid X Receptor alpha; D051028:bcl-2-Associated X Protein; C062495:oncogene protein E7, Human papillomavirus type 6