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Prognostic Significance of Metastasis-Associated Protein S100A4 (Mts1) in Prostate Cancer Progression and Chemoprevention Regimens in an Autochthonous Mouse Model

¹ Department of Dermatology, University of Wisconsin-Madison, Wisconsin and ² Department of Urology, Case Western Reserve University and the University Hospitals of Cleveland, Cleveland, Ohio

Requests for reprints: Hasan Mukhtar, Department of Dermatology, University of Wisconsin, 1300 University Avenue, Medical Sciences Center, B-25, Madison, WI 53706. Phone: 608-263-3927; Fax: 608-263-5223; E-mail: hmukhtar{at}wisc.edu.

Purpose: We recently showed that metastasis-promoting Mts1 gene (S100A4) and protein is overexpressed during progression of prostate cancer in humans. The purpose of this study was to assess the expression of S100A4 during autochthonous prostate cancer progression in transgenic adenocarcinoma of the mouse prostate (TRAMP) model. Because oral consumption of green tea polyphenols (GTP) has been shown to inhibit metastasis and prostate cancer in TRAMP, we further assessed the significance of S100A4 during chemoprevention regimen.

Experimental Design: Male TRAMP mice 8 weeks of age were equally divided into two groups. A freshly prepared 0.1% GTP solution in tap water was supplied thrice a week to experimental animals as the sole source of drinking fluid for 24 weeks, whereas the control group of animals received the same tap water throughout the experiment. The animals were sacrificed at 0, 8, 16, and 24 weeks of GTP feeding and were analyzed for S100A4 and E-cadherin. Additional untreated and treated nontransgenic controls were also included in the study.

Results: With the progression of age and prostate cancer growth in TRAMP mice, an increase in the expression of S100A4 at mRNA and protein level in dorsolateral prostate, but not in nontransgenic mice, occurred. GTP feeding to TRAMP mice resulted in marked inhibition of prostate cancer progression, which was associated with reduction of S100A4 and restoration of E-cadherin.

Conclusions: S100A4 represents a promising marker for prostate cancer progression and could be employed as a biomarker in chemoprevention regimens.

Key Words: TRAMP • S100A4 • E-cadherin • prostate cancer • green tea • chemoprevention

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