title: A Mouse Model of Hyperproliferative Human Epithelium Validated by Keratin Profiling Shows an Aberrant Cytoskeletal Response to Injury.
abstract: A validated animal model would assist with research on the immunological consequences of the chronic expression of stress keratins KRT6, KRT16, and KRT17, as observed in human pre-malignant hyperproliferative epithelium. Here we examine keratin gene expression profile in skin from mice expressing the E7 oncoprotein of HPV16 (K14E7) demonstrating persistently hyperproliferative epithelium, in nontransgenic mouse skin, and in hyperproliferative actinic keratosis lesions from human skin. We demonstrate that K14E7 mouse skin overexpresses stress keratins in a similar manner to human actinic keratoses, that overexpression is a consequence of epithelial hyperproliferation induced by E7, and that overexpression further increases in response to injury. As stress keratins modify local immunity and epithelial cell function and differentiation, the K14E7 mouse model should permit study of how continued overexpression of stress keratins impacts on epithelial tumor development and on local innate and adaptive immunity.
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Samal
authors.initials: S
authors.lastname: Zhussupbekova
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Rohit
authors.initials: R
authors.lastname: Sinha
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Paula
authors.initials: P
authors.lastname: Kuo
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, USA.
authors.forename: Paul F
authors.initials: PF
authors.lastname: Lambert
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia. Electronic address: i.frazer@uq.edu.au.
authors.forename: Ian H
authors.initials: IH
authors.lastname: Frazer
authors.affiliation: The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia.
authors.forename: Zewen K
authors.initials: ZK
authors.lastname: Tuong
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D003599:Cytoskeleton / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D052162:Human papillomavirus 16 / Q000235:genetics; D006801:Humans; D053547:Keratin-14 / Q000235:genetics; D007633:Keratins / Q000378:metabolism*; D007642:Keratosis / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D050725:Papillomavirus E7 Proteins / Q000235:genetics; D011401:Promoter Regions, Genetic; D012867:Skin / Q000378:metabolism*; D014184:Transplantation, Homologous
chemical_list: D053547:Keratin-14; D050725:Papillomavirus E7 Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; D007633:Keratins
keywords: E7; HPV16; Hyperplasia; Keratins