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Suppression of PTEN Transcription by UVA
Author(s) -
Zhao Baozhong,
Ming Mei,
He YuYing
Publication year - 2013
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21451
Subject(s) - pten , transcription (linguistics) , chemistry , microbiology and biotechnology , transcription factor , biology , biochemistry , signal transduction , gene , pi3k/akt/mtor pathway , linguistics , philosophy
Although ultraviolet A ( UVA ; 315–400 nm) has different physical and biological targets than ultraviolet B (UVB; 280–315 nm), the contribution of UVA to skin cancer susceptibility and its molecular basis remain largely unknown. Here we show that chronic UVA radiation suppresses phosphatase and tensin homolog ( PTEN ) expression at the m RNA level. Subchronic and acute UVA radiation also downregulated PTEN in normal human epidermal keratinocytes, skin culture, and mouse skin. At the molecular level, chronic UVA radiation decreased the transcriptional activity of the PTEN promoter in a methylation‐independent manner, whereas it had no effect on the protein stability or m RNA stability of PTEN . In contrast, we found that UVA ‐induced activation of the Ras/ ERK / AKT and NF ‐к B pathways plays an important role in UV ‐induced PTEN downregulation. Inhibiting extracellular signal‐regulated kinases ( ERK ) or protein pinase B (AKT) increases PTEN expression. Our findings may provide unique insights into PTEN downregulation as a critical component of UVA 's molecular impact during keratinocyte transformation. © 2012 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:184‐191, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21451