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dc.contributor.authorEinspahr, Janine G.
dc.contributor.authorCuriel-Lewandrowski, Clara
dc.contributor.authorCalvert, Valerie S.
dc.contributor.authorStratton, Steven P.
dc.contributor.authorAlberts, David S.
dc.contributor.authorWarneke, James
dc.contributor.authorHu, Chengcheng
dc.contributor.authorSaboda, Kathylynn
dc.contributor.authorWagener, Elisabeth L.
dc.contributor.authorDickinson, Sally
dc.contributor.authorDong, Zigang
dc.contributor.authorBode, Ann M.
dc.contributor.authorPetricoin, Emanuel F.
dc.date.accessioned2017-11-22T19:04:23Z
dc.date.available2017-11-22T19:04:23Z
dc.date.issued2017-09-21
dc.identifier.citationProtein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light 2017, 1 (1) npj Precision Oncologyen
dc.identifier.issn2397-768X
dc.identifier.doi10.1038/s41698-017-0037-7
dc.identifier.urihttp://hdl.handle.net/10150/626116
dc.description.abstractUltraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL. RPPA analysis was used to map the altered cell signaling networks resulting from acute doses of solar simulated radiation (SSL). To that end, we exposed sun-protected skin in volunteers to acute doses of two MED of SSL and collected biopsies pre-SSL and post-SSL irradiation. Frozen biopsies were subjected to laser capture microdissection (LCM) and then assessed by RPPA. The activation/phosphorylation or total levels of 128 key signaling proteins and drug targets were selected for statistical analysis. Coordinate network-based analysis was performed on specific signaling pathways that included the PI3k/Akt/mTOR and Ras/Raf/MEK/ERK pathways. Overall, we found early and sustained activation of the PI3K-AKT-mTOR and MAPK pathways. Cell death and apoptosis-related proteins were activated at 5 and 24 h. Ultimately, expression profile patterns of phosphorylated proteins in the epidermal growth factor receptor (EGFR), AKT, mTOR, and other relevant pathways may be used to determine pharmacodynamic activity of new and selective topical chemoprevention agents administered in a test area exposed to SSL to determine drug-induced attenuation or reversal of skin carcinogenesis pathways.
dc.description.sponsorshipNational Cancer Institute, National Institutes of Health [P01 CA027502, K07 CA132956, P30 CA023074]en
dc.language.isoenen
dc.publisherNATURE PUBLISHING GROUPen
dc.relation.urlhttp://www.nature.com/articles/s41698-017-0037-7en
dc.rights© The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleProtein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated lighten
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Ctr Cancen
dc.contributor.departmentUniv Arizona, Dept Meden
dc.contributor.departmentUniv Arizona, Dept Surgen
dc.contributor.departmentUniv Arizona, Dept Epidemiol & Biostaten
dc.identifier.journalNPJ Precision Oncologyen
dc.description.note6 month embargo; Published online: 21 September 2017.en
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
dc.eprint.versionFinal accepted manuscripten
refterms.dateFOA2018-09-12T00:11:45Z
html.description.abstractUltraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL. RPPA analysis was used to map the altered cell signaling networks resulting from acute doses of solar simulated radiation (SSL). To that end, we exposed sun-protected skin in volunteers to acute doses of two MED of SSL and collected biopsies pre-SSL and post-SSL irradiation. Frozen biopsies were subjected to laser capture microdissection (LCM) and then assessed by RPPA. The activation/phosphorylation or total levels of 128 key signaling proteins and drug targets were selected for statistical analysis. Coordinate network-based analysis was performed on specific signaling pathways that included the PI3k/Akt/mTOR and Ras/Raf/MEK/ERK pathways. Overall, we found early and sustained activation of the PI3K-AKT-mTOR and MAPK pathways. Cell death and apoptosis-related proteins were activated at 5 and 24 h. Ultimately, expression profile patterns of phosphorylated proteins in the epidermal growth factor receptor (EGFR), AKT, mTOR, and other relevant pathways may be used to determine pharmacodynamic activity of new and selective topical chemoprevention agents administered in a test area exposed to SSL to determine drug-induced attenuation or reversal of skin carcinogenesis pathways.


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© The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.
Except where otherwise noted, this item's license is described as © The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.