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https://hdl.handle.net/2440/34690
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Type: | Journal article |
Title: | The histone deacetylase inhibitor SAHA arrests cancer cell growth, up-regulates thioredoxin-binding protein-2, and down-regulates thioredoxin |
Author: | Butler, L. Zhou, X. Marks, P. Rifkind, R. Richon, V. |
Citation: | Proceedings of the National Academy of Sciences of USA, 2002; 99(18):11700-11705 |
Publisher: | Natl Acad Sciences |
Issue Date: | 2002 |
ISSN: | 0027-8424 1091-6490 |
Statement of Responsibility: | 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 Vorinostat |
Description: | Copyright © 2002 by the National Academy of Sciences |
DOI: | 10.1073/pnas.182372299 |
Published version: | http://dx.doi.org/10.1073/pnas.182372299 |
Appears in Collections: | Aurora harvest 6 Medicine publications |
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