title: Basal cell carcinomas arise from hair follicle stem cells in Ptch1(+/-) mice.
abstract: Basal cell carcinomas (BCCs) are hedgehog-driven tumors that resemble follicular and interfollicular epidermal basal keratinocytes and hence long have been thought to arise from these cells. However, the actual cell of origin is unknown. Using cell fate tracking of X-ray induced BCCs in Ptch1(+/-) mice, we found their essentially exclusive origin to be keratin 15-expressing stem cells of the follicular bulge. However, conditional loss of p53 not only enhanced BCC carcinogenesis from the bulge but also produced BCCs from the interfollicular epidermis, at least in part by enhancing Smo expression. This latter finding is consistent with the lack of visible tumors on ears and tail, sites lacking Smo expression, in Ptch1(+/-) mice.
authors.affiliation: Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way, Oakland, CA 94609, USA.
authors.forename: Grace Ying
authors.initials: GY
authors.lastname: Wang
authors.forename: Joy
authors.initials: J
authors.lastname: Wang
authors.forename: Maria-Laura
authors.initials: ML
authors.lastname: Mancianti
authors.forename: Ervin H
authors.initials: EH
authors.lastname: Epstein
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D002280:Basal Cell Carcinoma / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D004817:Epidermis / Q000473:pathology / Q000528:radiation effects; D018859:Hair Follicle / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D006579:Heterozygote; D053547:Keratin-14 / Q000235:genetics / Q000378:metabolism; D053569:Keratin-15 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D000072086:Smoothened Receptor; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014965:X-Rays
chemical_list: D001426:Bacterial Proteins; C534700:Ccnb1 protein, mouse; D056744:Cyclin B1; D053547:Keratin-14; D053569:Keratin-15; C507446:Krt14 protein, mouse; C492053:Krt15 protein, mouse; D008164:Luminescent Proteins; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D016159:Tumor Suppressor Protein p53; C054562:yellow fluorescent protein, Bacteria