World J Mens Health.  2013 Apr;31(1):36-46.

Clinical Significance of Wnt/beta-Catenin Signalling and Androgen Receptor Expression in Prostate Cancer

• Jung SJ
• Oh S
• Lee GT
• Chung J
• Min K
• Yoon J
• Kim W
• Ryu DS
• Kim IY
• Kang DI

Abstract

PURPOSE
To investigate the relationships among the Wnt/beta-catenin pathway, androgen receptor (AR), and clinicopathological factors in hormone-naive prostate cancer.
MATERIALS AND METHODS
This study was conducted with132 cases of hormone-naive prostate cancer treated by prostatectomy and prostate needle biopsy. An immunohistochemical study using antibodies against beta-catenin, matrix metalloproteinase-7 (MMP-7), and the AR was performed. For the in vitro study, PC-3, LNCaP, 22Rv1, and DU145 cell lines were used.
RESULTS
The clinical or pathological stage ware a localized cancer in 36 patients (27.3%), locally advanced cancer in 31 (23.5%), and metastatic cancer in 65 (49.2%). We detected increased beta-catenin, AR, and MMP-7 expression with a high Gleason grade, disease progression, and increasing serum prostate-specific antigen (PSA) levels (p<0.01). In Spearman's rank correlations, the expression of cytoplasmic beta-catenin, MMP-7, and the AR were found to be significantly positively correlated. In addition, the expression of beta-catenin, MMP-7, and the AR were significantly correlated with clinicopathological variables indicative of a poor prognosis. Forty-nine patients with primary androgen deprivation had short response durations from hormone therapy to PSA progression with elevated MMP-7 expression on the Kaplan-Meier curve (p=0.0036).
CONCLUSIONS
These data show that an activated Wnt/beta-catenin pathway and AR expression in prostate cancer are correlated with metastasis and aggressiveness. In addition, the expression of MMP-7 protein, a target of the Wnt/beta-catenin pathway, is associated with PSA progression in prostate cancer patients undergoing primary hormone therapy.

Keyword

Prostate neoplasms; Beta catenin; Matrix metalloproteinases; Receptors, androgen; Prognosis

MeSH Terms

Antibodies
beta Catenin
Biopsy, Needle
Cell Line
Cytoplasm
Disease Progression
Humans
Matrix Metalloproteinase 7
Matrix Metalloproteinases
Neoplasm Metastasis
Prognosis
Prostate
Prostate-Specific Antigen
Prostatectomy
Prostatic Neoplasms
Receptors, Androgen
Antibodies
Matrix Metalloproteinase 7
Matrix Metalloproteinases
Prostate-Specific Antigen
Receptors, Androgen
beta Catenin

Figure

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  Fig. 1 In vitro, activation of the canonical Wnt pathway (Wnt3a-CM) led to translocation of β-catenin and the androgen receptor to the nucleus (A), and increased MMP-7 mRNA expression in prostate cancer cells (B). Wnt3a-CM: Wnt3a-conditioned medium, MMP: matrix metalloproteinase.

• 

  Fig. 2 Expression of β-catenin. β-catenin was expressed in both the membrane and cytoplasm of cancer cells (A: ×200). Cytoplasmic β-catenin expression was significantly correlated with a high Gleason grade (GG), high preoperative prostate-specific antigen (PSA), and disease progression (p<0.01) (B~D).

• 

  Fig. 3 Expression of matrix metalloproteinase-7 (MMP-7). MMP-7 was expressed in the nuclei of cancer cells (A: ×200). MMP-7 expression was significantly correlated with a high Gleason grade (GG), high preoperative prostate-specific antigen (PSA), and disease progression (p<0.01) (B~D).

• 

  Fig. 4 Expression of the androgen receptor (AR). The AR was expressed in the nuclei of cancer cells and cytoplasm (A: ×200). AR expression was significantly correlated with a high Gleason grade (GG), high preoperative prostate-specific antigen (PSA), and disease progression (p<0.01) (B~D).

• 

  Fig. 5 Relationships among the expression of β-catenin, matrix metalloproteinase-7 (MMP-7), and androgen receptor (AR) and prostate-specific antigen (PSA) progression after primary hormone therapy. Cases with moderate-to-strong MMP-7 expression exhibited rapid PSA progression. (A) β-catenin, (B) MMP-7, (C) AR.

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