title: Retinoic acid metabolism proteins are altered in trichoblastomas induced by mouse papillomavirus 1.
abstract: Skin cancer burden is significant as treatment costs have skyrocketed to $8.1 million annually and some forms metastasize, such as cutaneous squamous cell carcinoma (cSCC) and melanoma. cSCC is caused by altered growth factor signaling induced by chemical carcinogens, ultraviolet light (UV) exposure, and infections with papillomaviruses (PVs). One of the few options for preventing cSCC in high-risk patients is oral retinoids. While much is understood about retinoid treatments and metabolism in mouse models of chemically and UV exposure induced cSCC, little is known about the role of retinoids in PV-induced cSCC. To better understand how retinoid metabolism is altered in cSCC, we examined the expression of this pathway in the newly discovered mouse papillomavirus (MmuPV1), which produces trichoblastomas in dorsal skin but not cSCC. We found significant increases in a rate-limiting enzyme involved in retinoic acid synthesis and retinoic acid binding proteins, suggestive of increased RA synthesis, in MmuPV1-induced tumors in B6.Cg-Foxn1(nu)/J mice. Similar increases in these proteins were seen after acute UVB exposure in Crl:SKH1-Hr(hr) mice and in regressing pre-cancerous lesions in a chemically-induced mouse model, suggesting a common mechanism in limiting the progression of papillomas to full blown cSCC.
authors.affiliation: Department of Human Sciences (Nutrition), The Ohio State University, Columbus, OH, United States. Electronic address: everts.1@osu.edu.
authors.forename: Helen B
authors.initials: HB
authors.lastname: Everts
authors.affiliation: Department of Human Sciences (Nutrition), The Ohio State University, Columbus, OH, United States.
authors.forename: Liye
authors.initials: L
authors.lastname: Suo
authors.affiliation: The James Graham Brown Cancer Center, The University of Louisville, Louisville, KY, United States.
authors.forename: Shinge
authors.initials: S
authors.lastname: Ghim
authors.affiliation: The James Graham Brown Cancer Center, The University of Louisville, Louisville, KY, United States.
authors.forename: A
authors.initials: A
authors.lastname: Bennett Jenson
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Sundberg
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000150:complications*; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D014212:Tretinoin
keywords: Mouse papillomavirus; Retinoid metabolism; Trichoblastomas