Activation of the PI3K/Akt/mTOR and MAPK signaling pathways in response to acute solar-simulated light exposure of human skin

Yira Bermudez, Steven P. Stratton, Clara Curiel-Lewandrowski, James Warneke, Chengcheng Hu, George T. Bowden, Sally E. Dickinson, Zigang Dong, Ann M. Bode, Kathylynn Saboda, Christine A. Brooks, Emanuel F. Petricoin, Craig A. Hurst, David S. Alberts, Janine G. Einspahr

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

The incidence of skin cancer is higher than all other cancers and continues to increase, with an average annual cost over $8 billion in the United States. As a result, identifying molecular pathway alterations that occur with UV exposure to strategize more effective preventive and therapeutic approaches is essential. To that end, we evaluated phosphorylation of proteins within the PI3K/Akt and MAPK pathways by immunohistochemistry in sun-protected skin after acute doses of physiologically relevant solar-simulated ultraviolet light (SSL) in 24 volunteers. Biopsies were performed at baseline, 5 minutes, 1, 5, and 24 hours after SSL irradiation. Within the PI3K/Akt pathway, we found activation of Akt (serine 473) to be significantly increased at 5 hours while mTOR (serine 2448) was strongly activated early and was sustained over 24 hours after SSL. Downstream, we observed a marked and sustained increase in phospho-S6 (serine 235/S236), whereas phospho-4E-BP1 (threonines 37/46) was increased only at 24 hours. Within the MAPK pathway, SSL-induced expression of phospho-p38 (threonine 180/tyrosine 182) peaked at 1 to 5 hours. ERK 1/2 was observed to be immediate and sustained after SSL irradiation. Phosphorylation of histone H3 (serine 10), a core structural protein of the nucleosome, peaked at 5 hours after SSL irradiation. The expression of both p53 and COX-2 was increased at 5 hours and was maximal at 24 hours after SSL irradiation. Apoptosis was significantly increased at 24 hours as expected and indicative of a sunburn-type response to SSL. Understanding the timing of key protein expression changes in response to SSL will aid in development of mechanistic-based approaches for the prevention and control of skin cancers.

Original languageEnglish (US)
Pages (from-to)720-728
Number of pages9
JournalCancer Prevention Research
Volume8
Issue number8
DOIs
StatePublished - Aug 1 2015

Fingerprint Dive into the research topics of 'Activation of the PI3K/Akt/mTOR and MAPK signaling pathways in response to acute solar-simulated light exposure of human skin'. Together they form a unique fingerprint.

  • Cite this

    Bermudez, Y., Stratton, S. P., Curiel-Lewandrowski, C., Warneke, J., Hu, C., Bowden, G. T., Dickinson, S. E., Dong, Z., Bode, A. M., Saboda, K., Brooks, C. A., Petricoin, E. F., Hurst, C. A., Alberts, D. S., & Einspahr, J. G. (2015). Activation of the PI3K/Akt/mTOR and MAPK signaling pathways in response to acute solar-simulated light exposure of human skin. Cancer Prevention Research, 8(8), 720-728. https://doi.org/10.1158/1940-6207.CAPR-14-0407