Journal article
RNA Editing of Androgen Receptor Gene Transcripts in Prostate Cancer Cells
The Journal of biological chemistry, Vol.283(44), pp.29938-29949
10/31/2008
DOI: 10.1074/jbc.M800534200
PMCID: PMC2662061
PMID: 18708348
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 877T -> Again-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.
Details
- Title: Subtitle
- RNA Editing of Androgen Receptor Gene Transcripts in Prostate Cancer Cells
- Creators
- Harryl D. Martinez - University of California, DavisRohini J. Jasavala - Department of Pharmacology, University of California, Sacramento, California 95817Izumi Hinkson - University of California, DavisLatricia D. Fitzgerald - University of California, DavisJames S. Trimmer - University of California, DavisHsing-Jien Kung - University of California, DavisMichael E. Wright - University of California, Davis
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.283(44), pp.29938-29949
- DOI
- 10.1074/jbc.M800534200
- PMID
- 18708348
- PMCID
- PMC2662061
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 12
- Language
- English
- Date published
- 10/31/2008
- Academic Unit
- Molecular Physiology and Biophysics
- Record Identifier
- 9984297509802771
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