Abstract
Kruppel-like factor 6 (KLF6) is a zinc finger transcription factor of unknown function. Here, we show that the KLF6 gene is mutated in a subset of human prostate cancer. Loss-of-heterozygosity analysis revealed that one KLF6 allele is deleted in 77% (17 of 22) of primary prostate tumors. Sequence analysis of the retained KLF6 allele revealed mutations in 71% of these tumors. Functional studies confirm that whereas wild-type KLF6 up-regulates p21 (WAF1/CIP1) in a p53-independent manner and significantly reduces cell proliferation, tumor-derived KLF6 mutants do not. Our data suggest that KLF6 is a tumor suppressor gene involved in human prostate cancer.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alleles
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Amino Acid Substitution
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Animals
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Cell Division
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Cell Line
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Chromosome Mapping
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Chromosomes, Human, Pair 10 / genetics
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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Cyclins / metabolism
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Genes, Tumor Suppressor*
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Genetic Heterogeneity
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Humans
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Kruppel-Like Factor 6
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Kruppel-Like Transcription Factors
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Loss of Heterozygosity
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Male
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Mice
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Microsatellite Repeats
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Mutation*
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Mutation, Missense
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Proliferating Cell Nuclear Antigen / metabolism
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Promoter Regions, Genetic
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Prostatic Neoplasms / genetics*
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Proto-Oncogene Proteins*
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Trans-Activators / chemistry
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Trans-Activators / genetics*
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Trans-Activators / physiology
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Transcriptional Activation
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Tumor Cells, Cultured
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Up-Regulation
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Zinc Fingers
Substances
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CDKN1A protein, human
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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KLF6 protein, human
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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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Proliferating Cell Nuclear Antigen
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Proto-Oncogene Proteins
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Trans-Activators