Wnt/Β-Catenin activation promotes prostate tumor progression in a mouse model

X. Yu, Y. Wang, David Degraff, M. L. Wills, R. J. Matusik

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82 Citations (Scopus)

Abstract

Our previous studies have found that activation of Wnt/Β-catenin signaling resulted in mouse prostatic intraepithelial neoplasia (mPIN). In the large probasin promoter directed SV40-large T-antigen (LPB-Tag) expressing mouse prostate, mPIN forms with rare areas of adenocarcinoma. Combining expression of both Wnt-signaling and Tag expression in the mouse prostate, we have studied the role of Wnt/Β-catenin signaling in the progression from mPIN to adenocarcinoma. Our results show that the prostates of mice expressing Tag alone or nuclear Β-catenin alone developed mPIN, whereas the activation of both Tag and the Wnt/Β-catenin pathway resulted in invasive prostate adenocarcinoma. Furthermore, Foxa2, a forkhead transcription factor, was induced by active Wnt/Β-catenin signaling, and the expression of Foxa2 was associated with the invasive phenotype in the primary prostate cancer. In the LPB-Tag/dominant active (DA) Β-catenin prostates, MMP7, a Wnt/Β-catenin target gene, was upregulated. Furthermore, we also assessed AR and AR signaling pathway in these LPB-Tag/DA Β-catenin mice. Although Β-catenin is a well-known AR co-activator in vitro, our study provides strong in vivo evidences indicating that both AR protein and the AR pathway were downregulated in the prostate of LPB-Tag/DA Β-catenin mice. Histological analysis shows that prostate sections derived from the LPB-Tag/DA Β-catenin mice display neuroendocrine differentiation (NED), but NE cancer does not develop. Together, our findings indicate that Wnt/Β-catenin signaling has an important role in the progression of mPIN to prostate adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)1868-1879
Number of pages12
JournalOncogene
Volume30
Issue number16
DOIs
StatePublished - Apr 21 2011

Fingerprint

Catenins
Prostate
Prostatic Intraepithelial Neoplasia
Neoplasms
Adenocarcinoma
Forkhead Transcription Factors
Polyomavirus Transforming Antigens
Wnt Signaling Pathway
Viral Tumor Antigens
Prostatic Neoplasms
Down-Regulation

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Yu, X. ; Wang, Y. ; Degraff, David ; Wills, M. L. ; Matusik, R. J. / Wnt/Β-Catenin activation promotes prostate tumor progression in a mouse model. In: Oncogene. 2011 ; Vol. 30, No. 16. pp. 1868-1879.
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Wnt/Β-Catenin activation promotes prostate tumor progression in a mouse model. / Yu, X.; Wang, Y.; Degraff, David; Wills, M. L.; Matusik, R. J.

In: Oncogene, Vol. 30, No. 16, 21.04.2011, p. 1868-1879.

Research output: Contribution to journalArticle

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