Androgen-regulated genes differentially modulated by the androgen receptor coactivator L-dopa decarboxylase in human prostate cancer cells

Mol Cancer. 2007 Jun 6;6:38. doi: 10.1186/1476-4598-6-38.

Abstract

Background: The androgen receptor is a ligand-induced transcriptional factor, which plays an important role in normal development of the prostate as well as in the progression of prostate cancer to a hormone refractory state. We previously reported the identification of a novel AR coactivator protein, L-dopa decarboxylase (DDC), which can act at the cytoplasmic level to enhance AR activity. We have also shown that DDC is a neuroendocrine (NE) marker of prostate cancer and that its expression is increased after hormone-ablation therapy and progression to androgen independence. In the present study, we generated tetracycline-inducible LNCaP-DDC prostate cancer stable cells to identify DDC downstream target genes by oligonucleotide microarray analysis.

Results: Comparison of induced DDC overexpressing cells versus non-induced control cell lines revealed a number of changes in the expression of androgen-regulated transcripts encoding proteins with a variety of molecular functions, including signal transduction, binding and catalytic activities. There were a total of 35 differentially expressed genes, 25 up-regulated and 10 down-regulated, in the DDC overexpressing cell line. In particular, we found a well-known androgen induced gene, TMEPAI, which wasup-regulated in DDC overexpressing cells, supporting its known co-activation function. In addition, DDC also further augmented the transcriptional repression function of AR for a subset of androgen-repressed genes. Changes in cellular gene transcription detected by microarray analysis were confirmed for selected genes by quantitative real-time RT-PCR.

Conclusion: Taken together, our results provide evidence for linking DDC action with AR signaling, which may be important for orchestrating molecular changes responsible for prostate cancer progression.

Publication types

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

MeSH terms

  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / metabolism
  • Androgens*
  • Blotting, Western
  • Cell Line, Tumor / metabolism
  • Dopa Decarboxylase / genetics
  • Dopa Decarboxylase / physiology*
  • Enzyme Induction / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genetic Vectors / pharmacology
  • Humans
  • Male
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Neoplasms, Hormone-Dependent / enzymology*
  • Neoplasms, Hormone-Dependent / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / metabolism
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Receptors, Androgen / physiology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / physiology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tetracycline / pharmacology
  • Transfection

Substances

  • Androgens
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Androgen
  • Recombinant Fusion Proteins
  • Dopa Decarboxylase
  • Tetracycline