Journal Article

Expression of 15-lipoxygenase-1 is regulated by histone acetylation in human colorectal carcinoma

Hideki Kamitani, Seijiro Taniura, Hiroshi Ikawa, Takashi Watanabe, Uddhav P. Kelavkar and Thomas E. Eling

in Carcinogenesis

Volume 22, issue 1, pages 187-191
Published in print January 2001 | ISSN: 0143-3334
Published online January 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.1.187
Expression of 15-lipoxygenase-1 is regulated by histone acetylation in human colorectal carcinoma

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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.

Keywords: FBS, fetal bovine serum; H4, histone 4; HDAC, histone deacetylase; 15-LO-1, 15-lipoxygenase-1; NaBT, sodium butyrate; TSA, trichostatin A.

Journal Article.  3264 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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