Abstract
In the periphery, a galectin-1 receptor, CD7, plays crucial roles in galectin-1-mediated apoptosis of activated T-cells as well as progression of T-lymphoma. Previously, we demonstrated that NF-kappaB downregulated CD7 gene expression through the p38 MAPK pathway in developing immature thymocytes. However, its regulatory pathway is not well understood in functional mature T-cells. Here, we show that CD7 expression was downregulated by Twist2 in Jurkat cells, a human acute T-cell lymphoma cell line, and in EL4 cells, a mature murine T-cell lymphoma cell line. Furthermore, ectopic expression of Twist2 in Jurkat cells reduced galectin-1-induced apoptosis. While full-length Twist2 decreased CD7 promoter activity, a C-terminal deletion form of Twist2 reversed its inhibition, suggesting an important role of the C-terminus in CD7 regulation. In addition, CD7 expression was enhanced by histone deacetylase inhibitors such as trichostatin A and sodium butyrate, which indicates that Twist2 might be one of candidate factors involved in histone deacetylation. Based on these results, we conclude that upregulation of Twist2 increases the resistance to galectin-1-mediated-apoptosis, which may have significant implications for the progression of some T-cells into tumors such as Sezary cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD7 / genetics
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Antigens, CD7 / immunology
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Antigens, CD7 / metabolism*
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Apoptosis / drug effects
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Apoptosis / genetics
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Chromatin Assembly and Disassembly / drug effects
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Chromatin Assembly and Disassembly / genetics
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Disease Progression
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Galectin 1 / immunology
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Galectin 1 / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / genetics
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Gene Expression Regulation, Neoplastic / immunology
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Histone Deacetylase Inhibitors / pharmacology
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Humans
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Hydroxamic Acids / pharmacology
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Jurkat Cells
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Mice
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Protein Engineering
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Protein Structure, Tertiary / genetics
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Repressor Proteins / genetics
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Repressor Proteins / immunology
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Repressor Proteins / metabolism*
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Sequence Deletion
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Sezary Syndrome / genetics
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Sezary Syndrome / immunology*
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Sezary Syndrome / pathology
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Sezary Syndrome / physiopathology
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T-Lymphocyte Subsets / drug effects
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism*
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T-Lymphocytes / pathology
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Transfection
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Twist-Related Protein 1 / genetics
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Twist-Related Protein 1 / immunology
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Twist-Related Protein 1 / metabolism*
Substances
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Antigens, CD7
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Galectin 1
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Histone Deacetylase Inhibitors
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Hydroxamic Acids
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Repressor Proteins
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TWIST2 protein, human
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Twist-Related Protein 1
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trichostatin A