title: Decreased RARβ expression induces abundant inflammation and cervical precancerous lesions.
abstract: It is well known that vitamin A and its receptors protect against cancer development and that Retinoid Acid Receptor β (RARβ) is epigenetically silenced during tumoral progression. Cervical Cancer (CC) has been causally linked to high risk human papillomavirus (HR-HPV) infection. However, host factors are important in determining the outcome of persistent HR-HPV infection as most cervical precancerous lesions containing HR-HPVs do not progress to invasive carcinomas. Increasing evidence suggests that low diet in vitamin A and their receptors participate in the development of CC. The aim of this study has been to investigate the effects of abated RARβ expression in the development of cervical premalignant lesions in 4 month-old conditional mice (RARβ(L-/L-)). Results demonstrated the development of spontaneous squamous metaplasia, inflammatory infiltrate, enhanced mitotic activity, loss of cell differentiation, as well as decreased apoptosis and p16(INK4a) protein levels in RARβ(L-/L-) mice cervix. All these changes are hallmarks of moderate dysplasia. Importantly, our results suggest that the low expression of RARβ, may induce the down regulation of p16(INK4a), chronic inflammation and decreased apoptosis and may be involved in vulnerability to HR-HPV and early stage cervical carcinogenesis.
authors.affiliation: Department of Genetics & Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. San Pedro Zacatenco, 07360 México, DF, México.
authors.forename: M E
authors.initials: ME
authors.lastname: Albino-Sanchez
authors.affiliation: Department of Genetics & Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. San Pedro Zacatenco, 07360 México, DF, México.
authors.forename: J
authors.initials: J
authors.lastname: Vazquez-Hernandez
authors.affiliation: Department of Genetics & Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. San Pedro Zacatenco, 07360 México, DF, México.
authors.forename: R
authors.initials: R
authors.lastname: Ocadiz-Delgado
authors.affiliation: Department of Genetics & Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. San Pedro Zacatenco, 07360 México, DF, México.
authors.forename: N
authors.initials: N
authors.lastname: Serafin-Higuera
authors.affiliation: Department of Genetics & Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. San Pedro Zacatenco, 07360 México, DF, México.
authors.forename: I
authors.initials: I
authors.lastname: León-Galicia
authors.affiliation: Department of Genetics & Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. San Pedro Zacatenco, 07360 México, DF, México.
authors.forename: E
authors.initials: E
authors.lastname: Garcia-Villa
authors.affiliation: Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubiran (INCMNSZ), Vasco de Quiroga 15, Col. Seccion XVI, Tlalpan, 14000 México, DF, México.
authors.forename: R
authors.initials: R
authors.lastname: Hernandez-Pando
authors.affiliation: Department of Genetics & Molecular Biology, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Av. IPN 2508, Col. San Pedro Zacatenco, 07360 México, DF, México. Electronic address: vidal@cinvestav.mx.
authors.forename: P
authors.initials: P
authors.lastname: Gariglio
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D002584:Cervix Uteri / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011230:Precancerous Conditions / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D002578:Uterine Cervical Dysplasia / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology*; D014621:Vagina / Q000473:pathology
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta
keywords: Conditional mice; Inflammatory infiltrate; Moderate dysplasia; P16(INK4a); Retinoic acid receptor β; Squamous metaplasia