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

• Published in: Carcinogenesis (New York) 2001-01, Vol.22 (1), p.187-191
• Main Authors: Kamitani, Hideki, Taniura, Seijiro, Ikawa, Hiroshi, Watanabe, Takashi, Kelavkar, Uddhav P., Eling, Thomas E.
• Format: Article
• Language: English
• Subjects: 15-Lipoxygenase-1; 15-LO-1; Acetylation; Arachidonate 15-Lipoxygenase - biosynthesis; Arachidonate 15-Lipoxygenase - genetics; Biological and medical sciences; Blotting, Northern; Butyrates - pharmacology; Caco-2 Cells - enzymology; Colorectal Neoplasms - enzymology; Colorectal Neoplasms - genetics; Enzyme Inhibitors - pharmacology; FBS; fetal bovine serum; Gastroenterology. Liver. Pancreas. Abdomen; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; HDAC; histone 4; histone deacetylase; Histone Deacetylase Inhibitors; Histone Deacetylases - metabolism; Histones - metabolism; Humans; Hydroxamic Acids - pharmacology; Medical sciences; NaBT; Peptides, Cyclic - pharmacology; sodium butyrate; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; trichostatin A; TSA; Tumor Cells, Cultured; Tumors
• ISSN: 0143-3334; 1460-2180; 1460-2180
• DOI: 10.1093/carcin/22.1.187

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.