Activated androgen receptor downregulates E-cadherin gene expression and promotes tumor metastasis

Yan Nian Liu, Ying Liu, Han Jung Lee, Yung Hsiang Hsu, Ji Hshiung Chen

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

The loss of E-cadherin gene expression can cause the dysfunction of the cell-cell junction to trigger tumor metastasis. Members of the Snail family of transcription factors are repressors of the expression of the E-cadherin gene. In this study, we showed that the activated androgen receptor (AR) is a novel repressor of E-cadherin gene expression and can promote metastasis. Our results demonstrated that the activated AR could bind to the E-cadherin promoter in vitro and in vivo. The activated AR and HDAC1 had synergistic effects in downregulating E-cadherin gene expression. Treating cells with the AR ligand, dihydrotestosterone (DHT), triggered the reduction of E-cadherin expression and induced changes in cell morphology from an epithelial-like to a mesenchymal-like appearance. When nonmetastatic breast cancer cells expressing cytoplasmic AR were transplanted into mice and the mice were treated with DHT, tumors were detected at metastatic sites, whereas no tumors were detected in transplanted mice without DHT treatment. Furthermore, clinical data from breast cancer patients with invasive ductal carcinomas showed high levels of AR expression in the nuclei and low levels of E-cadherin expression. These results suggest that, similarly to Snail and Twist, the activated AR can downregulate E-cadherin expression to promote the activation of epithelial-mesenchymal transition and tumor metastasis.

Original languageEnglish
Pages (from-to)7096-7108
Number of pages13
JournalMolecular and Cellular Biology
Volume28
Issue number23
DOIs
Publication statusPublished - Dec 2008
Externally publishedYes

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Androgen Receptors
Cadherins
Down-Regulation
Neoplasm Metastasis
Gene Expression
Dihydrotestosterone
Neoplasms
Breast Neoplasms
Ductal Carcinoma
Epithelial-Mesenchymal Transition
Intercellular Junctions
Cytoplasmic and Nuclear Receptors
Epithelial Cells
Ligands
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Activated androgen receptor downregulates E-cadherin gene expression and promotes tumor metastasis. / Liu, Yan Nian; Liu, Ying; Lee, Han Jung; Hsu, Yung Hsiang; Chen, Ji Hshiung.

In: Molecular and Cellular Biology, Vol. 28, No. 23, 12.2008, p. 7096-7108.

Research output: Contribution to journalArticle

Liu, Yan Nian ; Liu, Ying ; Lee, Han Jung ; Hsu, Yung Hsiang ; Chen, Ji Hshiung. / Activated androgen receptor downregulates E-cadherin gene expression and promotes tumor metastasis. In: Molecular and Cellular Biology. 2008 ; Vol. 28, No. 23. pp. 7096-7108.
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