RNA editing of androgen receptor gene transcripts in prostate cancer cells

Harryl D. Martinez, Rohini J. Jasavala, Izumi Hinkson, Latricia D. Fitzgerald, James S. Trimmer, Hsing Jien Kung, Michael E. Wright

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Reactivation of the androgen receptor (AR) signaling pathway represents a critical step in the growth and survival of androgen-independent (AI) prostate cancer (CaP). In this study we show the DU145 and PC3 AI human CaP cell lines respond to androgens and require AR expression for optimal proliferation in vitro. Interestingly, AR gene transcripts in DU145 and PC3 cells harbored a large number of single base pair nucleotide transitions that resulted in missense mutations in selected AR codons. The most notable lesion detected in AR gene transcripts included the oncogenic codon 877T3→A gain-of-function mutation. Surprisingly, AR gene transcript nucleotide transitions were not genome-encoded substitutions, but instead the mutations co-localized to putative A-to-I, U-to-C, C-to-U, and G-to-A RNA editing sites, suggesting the lesions were mediated through RNA editing mechanisms. Higher levels of mRNA encoding the A-to-I RNA editing enzymes ADAR1 and ADARB1 were observed in DU145 and PC3 cells relative to the androgen-responsive LNCaP and 22Rv1 human CaP cell lines, which correlated with higher levels of AR gene transcript A-to-I editing detected in DU145 and PC3 cells. Our results suggest that AR gene transcripts are targeted by different RNA editing enzymes in DU145 and PC3 cells. Thus RNA editing of AR gene transcripts may contribute to the etiology of hormone-refractory phenotypes in advanced stage AI CaP.

Original languageEnglish
Pages (from-to)29938-29949
Number of pages12
JournalJournal of Biological Chemistry
Volume283
Issue number44
DOIs
Publication statusPublished - Oct 31 2008
Externally publishedYes

Fingerprint

RNA Editing
Androgen Receptors
Prostatic Neoplasms
Genes
Cells
RNA
Androgens
Codon
Nucleotides
Cell Line
Mutation
Missense Mutation
Enzymes
Base Pairing
Refractory materials
Substitution reactions
Genome
Hormones
Phenotype
Messenger RNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Martinez, H. D., Jasavala, R. J., Hinkson, I., Fitzgerald, L. D., Trimmer, J. S., Kung, H. J., & Wright, M. E. (2008). RNA editing of androgen receptor gene transcripts in prostate cancer cells. Journal of Biological Chemistry, 283(44), 29938-29949. https://doi.org/10.1074/jbc.M800534200

RNA editing of androgen receptor gene transcripts in prostate cancer cells. / Martinez, Harryl D.; Jasavala, Rohini J.; Hinkson, Izumi; Fitzgerald, Latricia D.; Trimmer, James S.; Kung, Hsing Jien; Wright, Michael E.

In: Journal of Biological Chemistry, Vol. 283, No. 44, 31.10.2008, p. 29938-29949.

Research output: Contribution to journalArticle

Martinez, HD, Jasavala, RJ, Hinkson, I, Fitzgerald, LD, Trimmer, JS, Kung, HJ & Wright, ME 2008, 'RNA editing of androgen receptor gene transcripts in prostate cancer cells', Journal of Biological Chemistry, vol. 283, no. 44, pp. 29938-29949. https://doi.org/10.1074/jbc.M800534200
Martinez HD, Jasavala RJ, Hinkson I, Fitzgerald LD, Trimmer JS, Kung HJ et al. RNA editing of androgen receptor gene transcripts in prostate cancer cells. Journal of Biological Chemistry. 2008 Oct 31;283(44):29938-29949. https://doi.org/10.1074/jbc.M800534200
Martinez, Harryl D. ; Jasavala, Rohini J. ; Hinkson, Izumi ; Fitzgerald, Latricia D. ; Trimmer, James S. ; Kung, Hsing Jien ; Wright, Michael E. / RNA editing of androgen receptor gene transcripts in prostate cancer cells. In: Journal of Biological Chemistry. 2008 ; Vol. 283, No. 44. pp. 29938-29949.
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