Journal
JOURNAL OF DERMATOLOGICAL SCIENCE
Volume 30, Issue 3, Pages 205-214Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0923-1811(02)00107-X
Keywords
glutathione S-transferase; antioxidant response element; human keratinocyte; human melanocyte; NF-kappa B; c-Ha-ras
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Funding
- NCI NIH HHS [P01CA27502] Funding Source: Medline
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Six families of glutathione S-transferases (GSTs), which play an important role in cellular detoxification, are identified in human cells. We report that human keratinocytes and melanocytes express significant levels of GST activity, for which GSTPI-1 is mainly responsible. But, in contrast to previous reports that GSTPI-1 level increases in skin tumor tissues, GSTPI-1 expression does not increase in transformed keratinocytes and melanocytes in culture. Although the human GSTP1 gene carries in its 5'-flanking region multiple copies of the antioxidant response element (ARE), no increase in GSTPI-1 expression was observed after treatment of human keratinocytes (HaCaT) with ARE-mediated inducers. ARE is a cis-acting DNA element and stimulates the transcription of many genes. While studies suggest that an NF-kappaB binding site in the promoter region might suppress the ARE function, such a mechanism does not appear to exist in HaCaT cells. Moreover, although ras has been shown to stimulate the expression of human GSTPI-1, the effect of c-Ha-ras on GSTPI-1 expression in HaCaT cells appears limited. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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