Role of p38 MAP kinases and ERK in mediating ultraviolet-B induced cyclooxygenase-2 gene expression in human keratinocytes

The roles of p38 MAP kinases and ERK in UVB induced cox-2 gene expression were studied in a human keratinocyte cell line, HaCaT. UVB significantly increased cox-2 gene expression at both protein and mRNA levels. As we reported previously, p38 and ERK were significantly activated after UVB irradiatio...

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Bibliographic Details
Published in:	Oncogene Vol. 20; no. 29; pp. 3921 - 3926
Main Authors:	WEIXING CHEN, OINGBO TANG, GONZALES, Melissa S, BOWDEN, G. Tim
Format:	Journal Article
Language:	English
Published:	Basingstoke Nature Publishing 28-06-2001 Nature Publishing Group
Subjects:	Biological and medical sciences Carcinogenesis Cell growth Cell Line Cell physiology Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes Cyclooxygenase 2 Enzymes Epigenetics ERK protein Extracellular signal-regulated kinase Fundamental and applied biological sciences. Psychology Gene expression Gene Expression Regulation - radiation effects Humans Isoenzymes - biosynthesis Isoenzymes - genetics Keratinocytes Keratinocytes - cytology Keratinocytes - radiation effects Kinases MEK inhibitors Membrane Proteins mitogen-activated protein kinase Mitogen-Activated Protein Kinases - antagonists & inhibitors Mitogen-Activated Protein Kinases - metabolism Molecular and cellular biology Oncology p38 Mitogen-Activated Protein Kinases p38 protein Phospholipases A - metabolism Prostaglandin-Endoperoxide Synthases - biosynthesis Prostaglandin-Endoperoxide Synthases - genetics Protein expression Proteins Radiation Skin cancer Tumors Ultraviolet radiation Ultraviolet Rays United States > US Arizona Human Prostaglandin-endoperoxide synthase Enzyme Induction Transferases Gene expression Carcinogenesis Cell line Gene Ultraviolet irradiation Protein kinase Keratinocyte Oxidoreductases
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Summary:	The roles of p38 MAP kinases and ERK in UVB induced cox-2 gene expression were studied in a human keratinocyte cell line, HaCaT. UVB significantly increased cox-2 gene expression at both protein and mRNA levels. As we reported previously, p38 and ERK were significantly activated after UVB irradiation in HaCaT cells. In addition, treating the cells with p38 inhibitor SB202190 or MEK inhibitor PD98059 specifically inhibited UVB induced p38 or ERK activation, respectively. In this study, we further examined the roles of p38 and ERK in UVB induced cox-2 gene expression in HaCaT cells. We found that SB202190 strongly inhibited UVB induced COX-2 protein expression at different time points and various UVB doses. Furthermore, SB202190 markedly inhibited UVB induced cox-2 mRNA. Our data indicated that ERK did not play a role in UVB induced cox-2 gene expression in human keratinocytes since suppression of ERK did not significantly alter UVB induced increase of COX-2 protein and mRNA. These results suggested, for the first time, that activation of p38 is required for UVB induced cox-2 gene expression in human keratinocytes. Since cox-2 expression plays an important role in UV carcinogenesis, p38 could be a potential molecular target for chemoprevention of skin cancer.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0950-9232 1476-5594
DOI:	10.1038/sj.onc.1204530