Journal
MOLECULAR CARCINOGENESIS
Volume 47, Issue 12, Pages 974-983Publisher
WILEY
DOI: 10.1002/mc.20450
Keywords
mRNA stability; Cox-2; AMPK; LKB1; skin carcinogenesis
Categories
Funding
- [CA27502]
- [CA 20374]
- [ES 06694]
- NATIONAL CANCER INSTITUTE [P01CA027502] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [P30ES006694] Funding Source: NIH RePORTER
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Considerable evidence has demonstrated that UVB irradiation is a strong carcinogen for nonmelanoma skin cancer. Up-regulation of cyclooxygenase -2 (Cox-2) has been shown to be a crucial event in human keratinocytes in their responses to UVB irradiation. To further understand the molecular mechanisms governing Cox-2 regulation, we found that UVB irradiation significantly increased Cox-2 mRNA stability by inducing cytoplasmic localization and protein abundance of human antigen R (HuR). We also found that AMP-activated kinase (AMPK) mediates these events and that UVB reduces AMPK activity by down-regulating LKB1 kinase. Finally, we propose a novel model in which UVB regulates Cox-2 mRNA stability through the LKB1/AMPK pathway. (C) 2008 Wiley-Liss, Inc.
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