PLZF regulates Pbx1 transcription and Pbx1-HoxC8 complex leads to androgen-independent prostate cancer proliferation

Prostate. 2006 Jul 1;66(10):1092-9. doi: 10.1002/pros.20443.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / physiology*
  • Blotting, Western
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Line, Tumor
  • Cell Proliferation
  • DNA, Neoplasm / analysis
  • DNA, Neoplasm / genetics
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / physiology*
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology
  • Genes, Tumor Suppressor / physiology
  • Homeodomain Proteins / analysis
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / physiology*
  • Humans
  • Kruppel-Like Transcription Factors
  • Male
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / genetics*
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplasms, Hormone-Dependent / physiopathology*
  • Oligonucleotide Array Sequence Analysis
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Promyelocytic Leukemia Zinc Finger Protein
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • Protein Binding
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology*
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / analysis
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic / physiology
  • Transfection

Substances

  • Androgens
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • HOXC8 protein, human
  • Homeodomain Proteins
  • Kruppel-Like Transcription Factors
  • Pre-B-Cell Leukemia Transcription Factor 1
  • Promyelocytic Leukemia Zinc Finger Protein
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • Transcription Factors
  • pbx1 protein, human
  • ZBTB16 protein, human