Abstract
Background:
Promyelocytic leukemia zinc finger (PLZF) protein, a transcriptional repressor and negative regulator of the cell cycle, has been characterized as a prostatic androgen-responsive gene. DU145 cells show androgen-independent growth and lack PLZF gene expression.
Methods:
We analyzed PLZF-regulating genes by DNA microarray using DU145 cells infected with LacZ- or PLZF-carrying adenoviruses.
Results:
DNA microarray revealed that Pbx1 is a prominent suppressed gene in PLZF-overexpressing DU145 cells. Androgen receptor (AR)-expressing DU145 cells recovered androgen-dependent PLZF expression and subsequent repression of Pbx1 expression. Immunoprecipitation of Pbx1 in DU145 cells revealed a Pbx1-HoxC8 heterocomplex. siRNAs for Pbx1 and HoxC8 knocked downexpression of each, and this suppressed androgen-independent cell growth. Double knockdown of both Pbx1 and HoxC8 suppressed cell growth much more significantly.
Conclusions:
Androgen-independent cell line DU145 cells lack PLZF gene expression, resulting in the upregulation of Pbx1 and HoxC8 expression. The Pbx1-HoxC8 heterocomplex may lead to androgen-independent growth in prostate cancer.
Copyright 2005 Wiley-Liss, Inc.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Androgens / physiology*
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Blotting, Western
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Cell Cycle / genetics
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Cell Cycle / physiology
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Cell Line, Tumor
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Cell Proliferation
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DNA, Neoplasm / analysis
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DNA, Neoplasm / genetics
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DNA-Binding Proteins / analysis
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DNA-Binding Proteins / genetics*
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DNA-Binding Proteins / physiology*
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Down-Regulation
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology
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Genes, Tumor Suppressor / physiology
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Homeodomain Proteins / analysis
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology*
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Humans
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Kruppel-Like Transcription Factors
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Male
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Neoplasms, Hormone-Dependent / chemistry
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Neoplasms, Hormone-Dependent / genetics*
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Neoplasms, Hormone-Dependent / pathology
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Neoplasms, Hormone-Dependent / physiopathology*
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Oligonucleotide Array Sequence Analysis
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Pre-B-Cell Leukemia Transcription Factor 1
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Promyelocytic Leukemia Zinc Finger Protein
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Prostatic Neoplasms / chemistry
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Prostatic Neoplasms / genetics*
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Prostatic Neoplasms / pathology
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Prostatic Neoplasms / physiopathology*
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Protein Binding
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Proto-Oncogene Proteins / analysis
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / physiology*
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RNA, Small Interfering / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / analysis
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Transcription Factors / genetics
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Transcription Factors / physiology*
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Transcription, Genetic / physiology
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Transfection
Substances
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Androgens
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DNA, Neoplasm
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DNA-Binding Proteins
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HOXC8 protein, human
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Homeodomain Proteins
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Kruppel-Like Transcription Factors
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Pre-B-Cell Leukemia Transcription Factor 1
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Promyelocytic Leukemia Zinc Finger Protein
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Proto-Oncogene Proteins
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RNA, Small Interfering
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Transcription Factors
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PBX1 protein, human
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ZBTB16 protein, human