Androgen depletion up-regulates cadherin-11 expression in prostate cancer

Yu Chen Lee, Chien Jui Cheng, Miao Huang, Mehmet A. Bilen, Xiangcang Ye, Nora M. Navone, Khoi Chu, Hsin Hsin Kao, Li Yuan Yu-Lee, Zhengxin Wang, Sue Hwa Lin

Research output: Contribution to journalArticle

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Abstract

Men with castration-resistant prostate cancer (PCa) frequently develop metastasis in bone. The reason for this association is unclear. We have previously shown that cadherin-11 (also known as OB-cadherin), a homophilic cell adhesion molecule that mediates osteoblast adhesion, plays a role in the metastasis of PCa to bone. Here, we report that androgen-deprivation therapy up-regulates cadherin-11 expression in PCa. In human PCa specimens, immunohistochemical staining showed that 22/26 (85%) primary PCa tumours from men with castrationresistant PCa expressed cadherin-11. In contrast, only 7/50 (14%) androgen-dependent PCa tumours expressed cadherin-11. In the MDA-PCa-2b xenograft animal model, cadherin-11 was expressed in the recurrent tumours following castration. In the PCa cell lines, there is an inverse correlation between expression of cadherin-11 and androgen receptor (AR), and cadherin-11 is expressed in very low levels or not expressed in AR-positive cell lines, including LNCaP, C4-2B4 and VCaP cells. We showed that AR likely regulates cadherin-11 expression in PCa through an indirect mechanism. Although re-expression of AR in the AR-negative PC3 cells led to the inhibition of cadherin-11 expression, depletion of androgen from the culture medium or down-regulation of AR by RNA interference in the C4-2B4 cells or VCaP cells only produced a modest increase of cadherin-11 expression. Promoter analysis indicated that cadherin-11 promoter does not contain a typical AR-binding element, and AR elicits a modest inhibition of cadherin-11 promoter activity, suggesting that AR does not regulate cadherin-11 expression directly. Together, these results suggest that androgen deprivation up-regulates cadherin-11 expression in prostate cancer, and this may contribute to the metastasis of PCa to bone. Our study suggests that therapeutic strategies that block cadherin-11 expression or function may be considered when applying androgen-ablation therapy.

Original languageEnglish
Pages (from-to)68-76
Number of pages9
JournalJournal of Pathology
Volume221
Issue number1
DOIs
Publication statusPublished - May 2010

Fingerprint

Androgens
Prostatic Neoplasms
Up-Regulation
Androgen Receptors
Bone Neoplasms
osteoblast cadherin
Castration
Neoplasm Metastasis
Cell Line
Neoplasms
Cell Adhesion Molecules
RNA Interference
Osteoblasts
Heterografts
Culture Media
Therapeutics
Down-Regulation
Animal Models

Keywords

  • Androgen receptor
  • Bone metastasis
  • Cadherin-11
  • Osteoblast
  • PCa

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Lee, Y. C., Cheng, C. J., Huang, M., Bilen, M. A., Ye, X., Navone, N. M., ... Lin, S. H. (2010). Androgen depletion up-regulates cadherin-11 expression in prostate cancer. Journal of Pathology, 221(1), 68-76. https://doi.org/10.1002/path.2687

Androgen depletion up-regulates cadherin-11 expression in prostate cancer. / Lee, Yu Chen; Cheng, Chien Jui; Huang, Miao; Bilen, Mehmet A.; Ye, Xiangcang; Navone, Nora M.; Chu, Khoi; Kao, Hsin Hsin; Yu-Lee, Li Yuan; Wang, Zhengxin; Lin, Sue Hwa.

In: Journal of Pathology, Vol. 221, No. 1, 05.2010, p. 68-76.

Research output: Contribution to journalArticle

Lee, YC, Cheng, CJ, Huang, M, Bilen, MA, Ye, X, Navone, NM, Chu, K, Kao, HH, Yu-Lee, LY, Wang, Z & Lin, SH 2010, 'Androgen depletion up-regulates cadherin-11 expression in prostate cancer', Journal of Pathology, vol. 221, no. 1, pp. 68-76. https://doi.org/10.1002/path.2687
Lee, Yu Chen ; Cheng, Chien Jui ; Huang, Miao ; Bilen, Mehmet A. ; Ye, Xiangcang ; Navone, Nora M. ; Chu, Khoi ; Kao, Hsin Hsin ; Yu-Lee, Li Yuan ; Wang, Zhengxin ; Lin, Sue Hwa. / Androgen depletion up-regulates cadherin-11 expression in prostate cancer. In: Journal of Pathology. 2010 ; Vol. 221, No. 1. pp. 68-76.
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