Protein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light
AuthorEinspahr, Janine G.
Calvert, Valerie S.
Stratton, Steven P.
Alberts, David S.
Wagener, Elisabeth L.
Bode, Ann M.
Petricoin, Emanuel F.
AffiliationUniv Arizona, Ctr Canc
Univ Arizona, Dept Med
Univ Arizona, Dept Surg
Univ Arizona, Dept Epidemiol & Biostat
MetadataShow full item record
PublisherNATURE PUBLISHING GROUP
CitationProtein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light 2017, 1 (1) npj Precision Oncology
JournalNPJ Precision Oncology
Rights© The Author(s) 2017. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License.
Collection InformationThis 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 email@example.com.
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.
Note6 month embargo; Published online: 21 September 2017.
VersionFinal published version
Final accepted manuscript
SponsorsNational Cancer Institute, National Institutes of Health [P01 CA027502, K07 CA132956, P30 CA023074]