Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors

Feng Sun, He Ge Chen, Wei Li, Xi Yang, Xin Wang, Richeng Jiang, Zhiyong Guo, Hegang Chen, Jiaoti Huang, Alexander D Borowsky, Yun Qiu

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Deregulation of androgen receptor (AR) splice variants has been implicated to play a role in prostate cancer development and progression. To understand their functions in prostate, we established a transgenic mouse model (AR3Tg) with targeted expression of the constitutively active and androgen-independent AR splice variant AR3 (a.k.a. AR-V7) in prostate epithelium. We found that overexpression of AR3 modulates expression of a number of tumor-promoting autocrine/paracrine growth factors (including Tgfβ2 and Igf1) and expands prostatic progenitor cell population, leading to development of prostatic intraepithelial neoplasia. In addition, we showed that some epithelial- mesenchymal transition-associated genes are up-regulated in AR3Tg prostates, suggesting that AR3 may antagonize AR activity and halt the differentiation process driven by AR and androgen. This notion is supported by our observations that the number of Ck5+/Ck8+ intermediate cells is increased in AR3Tg prostates after castration, and expression of AR3 transgene in these intermediate cells compromises prostate epithelium regeneration upon androgen replacement. Our results demonstrate that AR3 is a driver of prostate cancer, at least in part, through modulating multiple tumor-promoting autocrine/paracrine factors.

Original languageEnglish (US)
Pages (from-to)1529-1539
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number3
DOIs
StatePublished - Jan 17 2014

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Androgen Receptors
Prostate
Prostatic Neoplasms
Androgens
Tumors
Epithelium
Prostatic Intraepithelial Neoplasia
Epithelial-Mesenchymal Transition
Deregulation
Castration
Transgenes
Transgenic Mice
Regeneration
Neoplasms
Intercellular Signaling Peptides and Proteins
Stem Cells
Genes
Cells
Population

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors. / Sun, Feng; Chen, He Ge; Li, Wei; Yang, Xi; Wang, Xin; Jiang, Richeng; Guo, Zhiyong; Chen, Hegang; Huang, Jiaoti; Borowsky, Alexander D; Qiu, Yun.

In: Journal of Biological Chemistry, Vol. 289, No. 3, 17.01.2014, p. 1529-1539.

Research output: Contribution to journalArticle

Sun, Feng ; Chen, He Ge ; Li, Wei ; Yang, Xi ; Wang, Xin ; Jiang, Richeng ; Guo, Zhiyong ; Chen, Hegang ; Huang, Jiaoti ; Borowsky, Alexander D ; Qiu, Yun. / Androgen receptor splice variant AR3 promotes prostate cancer via modulating expression of autocrine/paracrine factors. In: Journal of Biological Chemistry. 2014 ; Vol. 289, No. 3. pp. 1529-1539.
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