Down-regulation of p57Kip2 induces prostate cancer in the mouse.
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.
Jin
Ren Jie
RJ
Vanderbilt Prostate Cancer Center and Department of Urologic Surgery, Vanderbilt University Medical Center, Nashville, Tenessee, USA.
Lho
Yongsoo
Y
Wang
Yongqing
Y
Ao
Mingfang
M
Revelo
Monica Patricia
MP
Hayward
Simon W
SW
Wills
Marcia L
ML
Logan
Susan K
SK
Zhang
Pumin
P
Matusik
Robert J
RJ
D000818:Animals; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D056741:Cyclin D; D051357:Cyclin-Dependent Kinase 2 / Q000096:biosynthesis; D051358:Cyclin-Dependent Kinase 4 / Q000096:biosynthesis; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000096:biosynthesis*; D016213:Cyclins / Q000096:biosynthesis; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000096:biosynthesis
C493965:Cdkn1c protein, mouse; D056741:Cyclin D; D050761:Cyclin-Dependent Kinase Inhibitor p57; D016213:Cyclins; D016160:Retinoblastoma Protein; C495893:Cdk2 protein, mouse; C495902:Cdk4 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4