Down-regulation of p57 Induces Prostate Cancer in the Mouse

p57 has been considered a candidate tumor suppressor gene because of its location in the genome, biochemical activities, and imprinting status. However, little is known about the role of p57 in tumorigenesis and cancer progression. Here, we show that the expression of p57 is significantly decreased in human prostate cancer, and the overexpression of p57 in prostate cancer cells significantly suppressed cell proliferation and reduced invasive ability. In addition, overexpression of p57 in LNCaP cells inhibited tumor formation in nude mice, resulting in well-differentiated squamous tumors rather than adenocarcinoma. Furthermore, the prostates of p57 knockout mice developed prostatic intraepithelial neoplasia and adenocarcinoma. Remarkably, this mouse prostate cancer is pathologically identical to human prostate adenocarcinoma. Therefore, these results strongly suggest that p57 is an important gene in prostate cancer tumorigenesis, and the p57 pathway may be a potential target for prostate cancer prevention and therapy. [Cancer Res 2008;68(10):3601–8]