Characterization of coordinated immediate responses by p16INK4A and p53 pathways in UVB-irradiated human skin cells.

Zakaria Y. Abd Elmageed, Rajiv L. Gaur, Mandy Williams, Mohamed E. Abdraboh, Prakash N. Rao, Madhwa H G Raj, Fathi M. Ismail, Allal Ouhtit

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

While the precise mechanisms of melanoma development are unknown, recent in vivo studies have revealed that the p16(Ink4a)/Rb pathway is disrupted in melanomagenesis. Here, we characterize the role of p16/Rb in coordinating the early events in UVB-irradiated skin. Foreskins and melanoma cell cultures were irradiated with low and high acute UVB doses and examined for cell-cycle- and apoptosis-associated genes. In melanoma cells, low UVB dose upregulated p16, p53, and p21 expression levels in Malme-3M, and high UVB dose accentuated the expression of p53 and p21(Cip1/Waf1), in particular; however, in SkMel-28 cells only p16 expression was upregulated in response to UV irradiation. In HaCaT cells, high UVB dose caused dramatic increase in p53 expression followed by upregulation of p21(Cip1/Waf1) and Bax, and downregulation of Bcl-2 leading to apoptosis. In HaCaT cells, reinstatement of p16 pathway restored cell-cycle arrest in response to low dose. Foreskin organ culture experiments confirmed our in vitro cell results. These data indicate that the p53 and p16 pathways respond independently to UVB insult. The p16 pathway is favored at low doses and results in cell-cycle arrest; the p53 pathway is more responsive to higher doses and induces apoptosis depending on p53 mutation status.

Original languageEnglish
Pages (from-to)175-183
Number of pages9
JournalThe Journal of investigative dermatology
Volume129
Issue number1
DOIs
Publication statusPublished - Jan 2009

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Skin
Cells
Apoptosis
Foreskin
Melanoma
Cell Cycle Checkpoints
Cell culture
Dosimetry
Genes
Irradiation
Organ Culture Techniques
Cell Cycle
Up-Regulation
Down-Regulation
Cell Culture Techniques
Experiments
Mutation

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Abd Elmageed, Z. Y., Gaur, R. L., Williams, M., Abdraboh, M. E., Rao, P. N., Raj, M. H. G., ... Ouhtit, A. (2009). Characterization of coordinated immediate responses by p16INK4A and p53 pathways in UVB-irradiated human skin cells. The Journal of investigative dermatology, 129(1), 175-183. https://doi.org/10.1038/jid.2008.208

Characterization of coordinated immediate responses by p16INK4A and p53 pathways in UVB-irradiated human skin cells. / Abd Elmageed, Zakaria Y.; Gaur, Rajiv L.; Williams, Mandy; Abdraboh, Mohamed E.; Rao, Prakash N.; Raj, Madhwa H G; Ismail, Fathi M.; Ouhtit, Allal.

In: The Journal of investigative dermatology, Vol. 129, No. 1, 01.2009, p. 175-183.

Research output: Contribution to journalArticle

Abd Elmageed, ZY, Gaur, RL, Williams, M, Abdraboh, ME, Rao, PN, Raj, MHG, Ismail, FM & Ouhtit, A 2009, 'Characterization of coordinated immediate responses by p16INK4A and p53 pathways in UVB-irradiated human skin cells.', The Journal of investigative dermatology, vol. 129, no. 1, pp. 175-183. https://doi.org/10.1038/jid.2008.208
Abd Elmageed, Zakaria Y. ; Gaur, Rajiv L. ; Williams, Mandy ; Abdraboh, Mohamed E. ; Rao, Prakash N. ; Raj, Madhwa H G ; Ismail, Fathi M. ; Ouhtit, Allal. / Characterization of coordinated immediate responses by p16INK4A and p53 pathways in UVB-irradiated human skin cells. In: The Journal of investigative dermatology. 2009 ; Vol. 129, No. 1. pp. 175-183.
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