Carcinogenesis, Vol. 22, No. 1, 187-191,
January 2001
© 2001 Oxford University Press
SHORT COMMUNICATION |
Expression of 15-lipoxygenase-1 is regulated by histone acetylation in human colorectal carcinoma
1 Laboratory of Molecular Carcinogenesis, National Institutes of Environmental Health Sciences, Research Triangle Park, NC 27709, USA,
2 Division of Neurosurgery, Institute of Neurological Sciences, Tottori University School of Medicine, 36-1 Nishi-cho, Yonago 683-0805, Japan and
3 Renal Division and Glomerulonephritis Center, Emory University, Atlanta, GA 30322, USA
15-Lipoxygenase-1 (15-LO-1) is expressed at higher levels in human colorectal tumors compared with normal tissue. 15-LO-1 is expressed in cultured human colorectal cells, but only after treatment with sodium butyrate (NaBT), which also stimulates apoptosis and cell differentiation. We examined the regulation of 15-LO-1 in human tissue and the colorectal carcinoma cell lines Caco-2 and SW-480 by treatment with histone deacetylase (HDAC) inhibitors: NaBT, trichostatin A (TSA) and HC toxin. Northern and western analysis showed that expression of 15-LO-1 was up-regulated by these HDAC inhibitors. Furthermore, HDAC inhibitors stimulated promoter activity of the 15-LO-1 gene ~12-to 21-fold using the –331/–23 region of the 15-LO-1 promoter, as measured with a luciferase–15-LO-1 promoter–reporter system, suggesting that 15-LO-1 is regulated at the transcriptional level by HDAC inhibitors. Histone proteins in colorectal cells were acetylated after treatment with HDAC inhibitors. Histone acetylation was also measured in human colorectal tissue and a correlation was observed between increased histone acetylation and 15-LO-1 expression. Thus, regulation of 15-LO-1 expression in colorectal tissues appears to occur by a novel and new mechanism associated with histone acetylation. Moreover, these results suggest that 15-LO-1 is a marker that reflects histone acetylation in colorectal carcinoma.
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