Modeling Truncated AR Expression in a Natural Androgen Responsive Environment and Identification of RHOB as a Direct Transcriptional Target

Hui Chi Tsai, David L. Boucher, Anthony Martinez, Clifford G Tepper, Hsing-Jien Kung

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Recent studies identifying putative truncated androgen receptor isoforms with ligand-independent activity have shed new light on the acquisition of androgen depletion independent (ADI) growth of prostate cancer. In this study, we present a model system in which a C-terminally truncated variant of androgen receptor (TC-AR) is inducibly expressed in LNCaP, an androgen-dependent cell line, which expresses little truncated receptor. We observed that when TC-AR is overexpressed, the endogenous full length receptor (FL-AR) is transcriptionally downmodulated. This in essence allows us to "replace" FL-AR with TC-AR and compare their individual properties in exactly the same genetic and cellular background, which has not been performed before. We show that the TC-AR translocates to the nucleus, activates transcription of AR target genes in the absence of DHT and is sufficient to confer ADI growth to the normally androgen dependent LNCaP line. We also show that while there is significant overlap in the genes regulated by FL- and TC-AR there are also differences in the respective suites of target genes with each AR form regulating genes that the other does not. Among the genes uniquely activated by TC-AR is RHOB which is shown to be involved in the increased migration and morphological changes observed in LN/TC-AR, suggesting a role of RHOB in the regulation of androgen-independent behavior of prostate cancer cells.

Original languageEnglish (US)
Article numbere49887
JournalPLoS One
Volume7
Issue number11
DOIs
StatePublished - Nov 29 2012

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Androgen Receptors
androgens
Androgens
Genes
prostatic neoplasms
genes
Prostatic Neoplasms
Cells
receptors
androgen receptors
Transcription
Growth
Protein Isoforms
transcription (genetics)
cell lines
Ligands
Cell Line

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Modeling Truncated AR Expression in a Natural Androgen Responsive Environment and Identification of RHOB as a Direct Transcriptional Target. / Tsai, Hui Chi; Boucher, David L.; Martinez, Anthony; Tepper, Clifford G; Kung, Hsing-Jien.

In: PLoS One, Vol. 7, No. 11, e49887, 29.11.2012.

Research output: Contribution to journalArticle

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