Early growth response gene 1 modulates androgen receptor signaling in prostate carcinoma cells

J Biol Chem. 2003 Oct 10;278(41):39906-11. doi: 10.1074/jbc.M307250200. Epub 2003 Jul 30.

Abstract

The transcription factor early growth response gene 1 (EGR1) has been implicated in diverse roles in the regulation of cell growth, apoptosis, and differentiation. Previous studies suggest that the effects of EGR1 on tumorigenesis are critically dependent on the cellular context. In a majority of prostate cancers, EGR1 is overexpressed and promotes prostate tumor progression. In contrast, in other tumor types such as breast cancers and glioblastomas, EGR1 is expressed at low levels and when overexpressed can inhibit tumor growth. To explore the role of EGR1 in prostate tumorigenesis, we examined the impact of EGR1 expression on the androgen receptor (AR) signaling pathway. We show here that EGR1 binds to the AR in prostate carcinoma cells, and an EGR1-AR complex can be detected by chromatin immunoprecipitation at the enhancer of an endogenous AR target gene. Overexpression of EGR1 enhanced AR-mediated transactivation, whereas EGR1 knockdown by small interfering RNA inhibited AR signaling pathway activity. Furthermore, Western blot and immunocytochemical analyses showed that constitutive overexpression of EGR1 promotes the translocation of AR from the cytoplasm to the nucleus. These results indicate that EGR1 may promote prostate cancer development by modulating the androgen receptor signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus
  • Base Sequence
  • Binding Sites
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Early Growth Response Protein 1
  • Humans
  • Immediate-Early Proteins*
  • Male
  • Prostate-Specific Antigen / genetics
  • Prostatic Neoplasms / etiology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism*
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Androgen / chemistry
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • DNA-Binding Proteins
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Immediate-Early Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Prostate-Specific Antigen