Down-regulation of p57Kip2 induces prostate cancer in the mouse.

Jin RJ, Lho Y, Wang Y, Ao M, Revelo MP, Hayward SW, Wills ML, Logan SK, Zhang P, Matusik RJ
Cancer Res. 2008 68 (10): 3601-8

PMID: 18483241 · DOI:10.1158/0008-5472.CAN-08-0073

p57(Kip2) 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(Kip2) in tumorigenesis and cancer progression. Here, we show that the expression of p57(Kip2) is significantly decreased in human prostate cancer, and the overexpression of p57(Kip2) in prostate cancer cells significantly suppressed cell proliferation and reduced invasive ability. In addition, overexpression of p57(Kip2) in LNCaP cells inhibited tumor formation in nude mice, resulting in well-differentiated squamous tumors rather than adenocarcinoma. Furthermore, the prostates of p57(Kip2) 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(Kip2) is an important gene in prostate cancer tumorigenesis, and the p57(Kip2) pathway may be a potential target for prostate cancer prevention and therapy.

MeSH Terms (16)

Animals Cell Differentiation Cell Line, Tumor Cell Transformation, Neoplastic Cyclin-Dependent Kinase 2 Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase Inhibitor p57 Cyclin D Cyclins Down-Regulation Gene Expression Regulation, Neoplastic Humans Male Mice Prostatic Neoplasms Retinoblastoma Protein

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