Second messenger up-regulation of androgen receptor gene transcription is absent in androgen insensitive human prostatic carcinoma cell lines, PC-3 and DU-145

FEBS Lett. 1996 Apr 1;383(3):237-40. doi: 10.1016/0014-5793(96)00241-4.

Abstract

A theoretical pathway of transcriptional regulation of the androgen receptor (AR) gene is via a cAMP response element (CRE) present in its promoter region (-508 to -501). After 20 h of stimulation with 8-bromo-cAMP, AR mRNA was upregulated in LNCaP but not in either PC-3 or DU-145 cell lines. We have demonstrated that the level of CRE binding protein (CREB) was the same in all cell lines and that the putative AR-CRE forms specific and compatible protein interactions with CREB. The ability to regulate AR gene transcription via the second messenger pathway is lost in the PC-3 and DU-145 cell lines. This may be an important primary mechanism of androgen insensitivity in prostate cancer.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cell Nucleus / metabolism
  • Cyclic AMP Response Element-Binding Protein / biosynthesis
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • DNA Primers
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Male
  • Molecular Sequence Data
  • Polymerase Chain Reaction
  • Prostatic Neoplasms
  • Protein Biosynthesis
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / isolation & purification
  • Rabbits
  • Receptors, Androgen / biosynthesis*
  • Reticulocytes / metabolism
  • Second Messenger Systems*
  • Transcription, Genetic*
  • Tumor Cells, Cultured
  • Up-Regulation

Substances

  • Cyclic AMP Response Element-Binding Protein
  • DNA Primers
  • RNA, Messenger
  • Receptors, Androgen