Abstract
The tumor suppressor Kruppel-like factor 6 (KLF6) is frequently inactivated in hepatocellular carcinoma (HCC). To unearth downstream transcriptional targets of KLF6, cDNA microarray analysis of whole liver was compared between KLF6+/+ and KLF6+/- mice. Pituitary tumor transforming gene 1 (PTTG1), an oncogene, was the most up-regulated transcript in KLF6+/- liver. In human HCCs, KLF6 mRNA was significantly decreased, associated with increased PTTG1. In HepG2, KLF6 transcriptionally repressed PTTG1 by direct promoter interaction. Whereas KLF6 downregulation by siRNA increased HepG2 proliferation, siRNA to PTTG1 was anti-proliferative. PTTG1 downregulation represents a novel tumor suppressor pathway of KLF6.
Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism
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Cell Line, Tumor
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Cell Proliferation
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Chromatin Immunoprecipitation
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Humans
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In Vitro Techniques
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Kruppel-Like Factor 6
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Kruppel-Like Transcription Factors / genetics
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Kruppel-Like Transcription Factors / metabolism*
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Liver Neoplasms / genetics
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Liver Neoplasms / metabolism
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Mice
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Mice, Mutant Strains
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Promoter Regions, Genetic / genetics
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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RNA, Small Interfering
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Reverse Transcriptase Polymerase Chain Reaction
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Securin
Substances
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Klf6 protein, mouse
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Kruppel-Like Factor 6
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Kruppel-Like Transcription Factors
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Neoplasm Proteins
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Securin
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pituitary tumor-transforming protein 1, human