title: A keratin 15 containing stem cell population from the hair follicle contributes to squamous papilloma development in the mouse.
abstract: The multistage model of nonmelanoma skin carcinogenesis has contributed significantly to our understanding of epithelial cancer in general. We used the Krt1-15CrePR1;R26R transgenic mouse to determine the contribution of keratin 15+ cells from the hair follicle to skin tumor development by following the labeled progeny of the keratin 15 expressing cells into papillomas. We present three novel observations. First, we found that keratin 15 expressing cells contribute to most of the papillomas by 20 weeks of promotion. Second, in contrast to the transient behavior of labeled keratin 15-derived progeny in skin wound healing, keratin 15 progeny persist in papillomas, and some malignancies for many months following transient induction of the reporter gene. Third, papillomas have surprising heterogeneity not only in their cellular composition, but also in their expression of the codon 61 signature Ha-ras mutation with approximately 30% of keratin 15-derived regions expressing the mutation. Together, these results demonstrate that keratin 15 expressing cells of the hair follicle contribute to cutaneous papillomas with long term persistence and a subset of which express the Ha-ras signature mutation characteristic of initiated cells.
authors.affiliation: Department of Dermatology, Columbia University Medical Center, New York, New York.
authors.forename: Shulan
authors.initials: S
authors.lastname: Li
authors.forename: Heuijoon
authors.initials: H
authors.lastname: Park
authors.forename: Carol S
authors.initials: CS
authors.lastname: Trempus
authors.forename: Derek
authors.initials: D
authors.lastname: Gordon
authors.forename: Yaping
authors.initials: Y
authors.lastname: Liu
authors.forename: George
authors.initials: G
authors.lastname: Cotsarelis
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Morris
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology*; D005260:Female; D011905:Genes, ras / Q000235:genetics; D018859:Hair Follicle / Q000187:drug effects / Q000473:pathology*; D006801:Humans; D019426:Integrases / Q000378:metabolism; D053569:Keratin-15 / Q000502:physiology*; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology; D061346:Laser Capture Microdissection; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D013234:Stem Cells / Q000187:drug effects / Q000473:pathology*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
chemical_list: D002273:Carcinogens; D053569:Keratin-15; D015127:9,10-Dimethyl-1,2-benzanthracene; C045073:Cre recombinase; D019426:Integrases; D013755:Tetradecanoylphorbol Acetate