PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation.
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.We analyzed PLZF-regulating genes by DNA microarray using DU145 cells infected with LacZ- or PLZF-carrying adenoviruses.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.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.
Mesh Terms:
Androgens, Blotting, Western, Cell Cycle, Cell Line, Tumor, Cell Proliferation, DNA, Neoplasm, DNA-Binding Proteins, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Homeodomain Proteins, Humans, Kruppel-Like Transcription Factors, Male, Neoplasms, Hormone-Dependent, Oligonucleotide Array Sequence Analysis, Prostatic Neoplasms, Protein Binding, Proto-Oncogene Proteins, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transcription, Genetic, Transfection
Androgens, Blotting, Western, Cell Cycle, Cell Line, Tumor, Cell Proliferation, DNA, Neoplasm, DNA-Binding Proteins, Down-Regulation, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, Homeodomain Proteins, Humans, Kruppel-Like Transcription Factors, Male, Neoplasms, Hormone-Dependent, Oligonucleotide Array Sequence Analysis, Prostatic Neoplasms, Protein Binding, Proto-Oncogene Proteins, RNA, Small Interfering, Reverse Transcriptase Polymerase Chain Reaction, Transcription Factors, Transcription, Genetic, Transfection
Prostate
Date: Jul. 01, 2006
PubMed ID: 16637071
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