Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo

  • Authors:
    • Y. S. Wan
    • Z. Q. Wang
    • Y. Shao
    • J. J. Voorhees
    • G. J. Fisher
  • View Affiliations

  • Published online on: March 1, 2001     https://doi.org/10.3892/ijo.18.3.461
  • Pages: 461-466
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Abstract

Growth factors interact with their cell surface receptors and activate the enzyme PI 3-kinase (PI 3-K) resulting in the formation of 3-phosphorylated phosphatidylinositols, which in turn activate the serine/threonine kinase AKT/PKB. AKT functions, in part, to promote cell survival by phosphorylating the BCL-2 family member BAD and the cell death pathway enzyme, caspase-9. Although induction of apoptosis by ultraviolet (UV) irradiation is well documented, little is known about UV activation of cell survival pathways in human skin cells. We have investigated whether UV activates the PI 3-K/AKT pathway in human skin in vivo. UV irradiation (2MED from UVB source) stimulated PI 3-kinase activity within 15 min. PI 3-K activity was maximal (2.5-fold, n=6) 30 min post UV and remained elevated for 4 h. UV stimulated AKT activity within 30 min. Maximal activity (4-fold, n=11) was observed 1 h post UV. UV also stimulated phosphorylation of the downstream AKT effectors, S6 kinase and BAD. S6 kinase was maximally stimulated 4 h post UV (15-fold, n=6). Increased BAD phosphorylation was observed 1 h post UV and remained elevated for 4 h. Western blot analysis revealed that UV-induced phosphorylation of BAD at Ser112, a site known to be phosphorylated by AKT. Inhibitors of EGFR and PI 3-kinase blocked UV-induced phosphorylation of BAD, suggesting that EGFR mediates UV-activated cell survival pathway. Collectively, both positive and negative roles for UV activation of the PI 3-K/AKT pathway in human skin can be envisioned. The PI 3-K/AKT pathway likely plays a critical role in balancing UV-induced apoptotic signals, thereby preventing widespread skin cell death. Conversely UV activation of the PI 3-K/AKT pathway may enhance survival of mutated cells, thereby promoting skin cancer, as has been found in several other types of cancer.

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March 2001
Volume 18 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Wan YS, Wang ZQ, Shao Y, Voorhees JJ and Fisher GJ: Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. Int J Oncol 18: 461-466, 2001
APA
Wan, Y.S., Wang, Z.Q., Shao, Y., Voorhees, J.J., & Fisher, G.J. (2001). Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo. International Journal of Oncology, 18, 461-466. https://doi.org/10.3892/ijo.18.3.461
MLA
Wan, Y. S., Wang, Z. Q., Shao, Y., Voorhees, J. J., Fisher, G. J."Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo". International Journal of Oncology 18.3 (2001): 461-466.
Chicago
Wan, Y. S., Wang, Z. Q., Shao, Y., Voorhees, J. J., Fisher, G. J."Ultraviolet irradiation activates PI 3-kinase/AKT survival pathway via EGF receptors in human skin in vivo". International Journal of Oncology 18, no. 3 (2001): 461-466. https://doi.org/10.3892/ijo.18.3.461