title: Deregulated expression of Cdc6 in the skin facilitates papilloma formation and affects the hair growth cycle.
abstract: Cdc6 encodes a key protein for DNA replication, responsible for the recruitment of the MCM helicase to replication origins during the G1 phase of the cell division cycle. The oncogenic potential of deregulated Cdc6 expression has been inferred from cellular studies, but no mouse models have been described to study its effects in mammalian tissues. Here we report the generation of K5-Cdc6, a transgenic mouse strain in which Cdc6 expression is deregulated in tissues with stratified epithelia. Higher levels of CDC6 protein enhanced the loading of MCM complexes to DNA in epidermal keratinocytes, without affecting their proliferation rate or inducing DNA damage. While Cdc6 overexpression did not promote skin tumors, it facilitated the formation of papillomas in cooperation with mutagenic agents such as DMBA. In addition, the elevated levels of CDC6 protein in the skin extended the resting stage of the hair growth cycle, leading to better fur preservation in older mice.
authors.affiliation: a DNA Replication Group; Molecular Oncology Program; Spanish National Cancer Reserch Center (CNIO) ; Madrid , Spain.
authors.forename: Sabela
authors.initials: S
authors.lastname: Búa
authors.affiliation: b Interdisciplinary Research Institute; Université Libre de Bruxelles ; Bruxelles , Belgium.
authors.forename: Peggy
authors.initials: P
authors.lastname: Sotiropoulou
authors.affiliation: a DNA Replication Group; Molecular Oncology Program; Spanish National Cancer Reserch Center (CNIO) ; Madrid , Spain.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Sgarlata
authors.affiliation: a DNA Replication Group; Molecular Oncology Program; Spanish National Cancer Reserch Center (CNIO) ; Madrid , Spain.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Borlado
authors.affiliation: c Cell Division and Cancer Group; Molecular Oncology Program; Spanish National Cancer Research Center (CNIO) ; Madrid , Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Eguren
authors.affiliation: d Genomics Unit, Biotechnology Program; Spanish National Cancer Research Center (CNIO) ; Madrid , Spain.
authors.forename: Orlando
authors.initials: O
authors.lastname: Domínguez
authors.affiliation: e Transgenic Mice Unit; Biotechnology Program; Spanish National Cancer Research Center (CNIO) ; Madrid , Spain.
authors.forename: Sagrario
authors.initials: S
authors.lastname: Ortega
authors.affiliation: c Cell Division and Cancer Group; Molecular Oncology Program; Spanish National Cancer Research Center (CNIO) ; Madrid , Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: Malumbres
authors.affiliation: b Interdisciplinary Research Institute; Université Libre de Bruxelles ; Bruxelles , Belgium.
authors.forename: Cedric
authors.initials: C
authors.lastname: Blanpain
authors.affiliation: a DNA Replication Group; Molecular Oncology Program; Spanish National Cancer Reserch Center (CNIO) ; Madrid , Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Méndez
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D053938:DNA Fragmentation; D004261:DNA Replication / Q000235:genetics / Q000502:physiology; D005260:Female; D006197:Hair / Q000378:metabolism*; D018859:Hair Follicle / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010212:Papilloma / Q000235:genetics / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics / Q000502:physiology
chemical_list: C502132:CDC6 protein, mouse; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins
keywords: Cdc6; DNA replication; hair follicle; mouse model; papilloma