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|Title:||The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin|
|Citation:||Proceedings of the National Academy of Sciences of the United States of America, 2002; 99(18):11700-11705|
|Publisher:||Natl Acad Sciences|
|Lisa M. Butler, Xianbo Zhou, Wei-Sheng Xu, Howard I. Scher, Richard A. Rifkind, Paul A. Marks, and Victoria M. Richon|
|Abstract:||Suberoylanilide hydroxamic acid (SAHA) is a potent inhibitor of histone deacetylases (HDACs) that causes growth arrest, differentiation, and/or apoptosis of many tumor types in vitro and in vivo. SAHA is in clinical trials for the treatment of cancer. HDAC inhibitors induce the expression of less than 2% of genes in cultured cells. In this study we show that SAHA induces the expression of vitamin D-up-regulated protein 1/thioredoxin-binding protein-2 (TBP-2) in transformed cells. As the expression of TBP-2 mRNA is increased, the expression of a second gene, thioredoxin, is decreased. In transient transfection assays, HDAC inhibitors induce TBP-2 promoter constructs, and this induction requires an NF-Y binding site. We report here that TBP-2 expression is reduced in human primary breast and colon tumors compared with adjacent tissue. These results support a model in which the expression of a subset of genes (i.e., including TBP-2) is repressed in transformed cells, leading to a block in differentiation, and culture of transformed cells with SAHA causes re-expression of these genes, leading to induction of growth arrest, differentiation, and/or apoptosis.|
|Keywords:||Tumor Cells, Cultured; Humans; Neoplasms; Hydroxamic Acids; Carrier Proteins; RNA, Messenger; DNA Primers; Enzyme Inhibitors; Cloning, Molecular; Cell Division; Apoptosis; Down-Regulation; Up-Regulation; Base Sequence; Molecular Sequence Data; Thioredoxins; Histone Deacetylase Inhibitors|
|Description:||Copyright © 2002 by the National Academy of Sciences|
|Appears in Collections:||Medicine publications|
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