Androgen-lnduced coactivator ANCCA mediates specific Androgen receptor signaling in prostate cancer

June X. Zou, Linlang Guo, Alexey S. Revenko, Clifford G. Tepper, Abigael T. Gemo, Hsing Jien Kung, Hong Wu Chen

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Androgen receptor (AR) plays a pivotal role in prostate cancer, primarily by regulating different gene expression programs elicited by androgen, which is important for cancer cell proliferation, survival, and differentiation. It is believed that the transcriptional function of AR is mediated largely by distinct nuclear coregulators. We report here the identification of ANCCA (also known as ATAD2), a new member of the AAA+ ATPase family proteins, as a novel AR coactivator. ANCCA interacts directly with AR and enhances its transcriptional activity, and is required for androgen-stimulated expression of a specific subgroup of genes including IGF1R, IRS-2, SGK1, and survivin. Upon androgen stimulation, ANCCA together with AR is recruited to the specific AR target genes. Suppression of ANCCA expression strongly inhibited the proliferation of androgen-responsive or androgenindependent, AR-positive prostate cancer cells and caused a significant increase of cellular apoptosis. Strikingly, the ANCCA gene itself, located at chromosome 8q24, is highly induced by androgen in androgen-dependent prostate cancer cells and xenograft tumors. Although ANCCA is hardly detected in normal human prostate tissue, high levels of ANCCA are found in hormone-independent prostate cancer cell lines, xenograft tumor, and a subset of prostate cancers with high Gleason scores. Together, these findings suggest that ANCCA plays an important role in prostate cancer by mediating specific AR functions in cancer cell survival and proliferation. The possession of ATPase and bromodomain by ANCCA makes it an attractive target for the development of therapeutics for the disease.

Original languageEnglish
Pages (from-to)3339-3346
Number of pages8
JournalCancer Research
Volume69
Issue number8
DOIs
Publication statusPublished - Apr 15 2009
Externally publishedYes

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Androgen Receptors
Androgens
Prostatic Neoplasms
Heterografts
Adenosine Triphosphatases
Cell Survival
Cell Proliferation
Genes
Neoplasms
Neoplasm Grading
Tumor Cell Line
Prostate
Cell Differentiation
Chromosomes
Hormones
Apoptosis
Gene Expression

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Androgen-lnduced coactivator ANCCA mediates specific Androgen receptor signaling in prostate cancer. / Zou, June X.; Guo, Linlang; Revenko, Alexey S.; Tepper, Clifford G.; Gemo, Abigael T.; Kung, Hsing Jien; Chen, Hong Wu.

In: Cancer Research, Vol. 69, No. 8, 15.04.2009, p. 3339-3346.

Research output: Contribution to journalArticle

Zou, June X. ; Guo, Linlang ; Revenko, Alexey S. ; Tepper, Clifford G. ; Gemo, Abigael T. ; Kung, Hsing Jien ; Chen, Hong Wu. / Androgen-lnduced coactivator ANCCA mediates specific Androgen receptor signaling in prostate cancer. In: Cancer Research. 2009 ; Vol. 69, No. 8. pp. 3339-3346.
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