An unusual gene dosage effect of p27kip1 in a mouse model of prostate cancer

被引：2

作者：

Abate-Shen, C

Shen, MM

机构：

[1] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA

[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Med, Piscataway, NJ 08854 USA

[3] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Canc Inst New Jersey, Dept Pediat, Piscataway, NJ 08854 USA

来源：

CELL CYCLE | 2005年 / 4卷 / 03期

关键词：

prostate cancer; p27(kip1); gene dosage; expression profiling; Cyclin D1; mouse models;

D O I：

10.4161/cc.4.3.1530

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Expression of the p27(kip1) cell cycle inhibitor is downregulated in a wide range of carcinomas, yet it is rarely inactivated completely. Our recent studies of a mouse model of prostate carcinogenesis have revealed that cancer progression is enhanced by a two-fold reduction in p27(kip1) gene dosage, but is unexpectedly inhibited by further decrease in p27(kip1) activity. This paradoxical finding may explain the unusual features of p27(kip1) downregulation in human cancer, and also suggests a potential route for therapeutic intervention.

引用

收藏

页码：426 / 428

页数：3

相关论文

共 17 条

[1] Deregulated homeobox gene expression in cancer: Cause or consequence? [J].

Abate-Shen, C .

NATURE REVIEWS CANCER, 2002, 2 (10) :777-785

[2] p27Kip1 modulates cell migration through the regulation of RhoA activation [J].

Besson, A ;

Gurian-West, M ;

Schmidt, A ;

Hall, A ;

Roberts, JM .

GENES & DEVELOPMENT, 2004, 18 (08) :862-876

[3] Deregulated degradation of the cdk inhibitor p27 and malignant transformation [J].

Bloom, J ;

Pagano, M .

SEMINARS IN CANCER BIOLOGY, 2003, 13 (01) :41-47

[4] The p21Cip1 and p27Kip1 CDK 'inhibitors' are essential activators of cyclin D-dependent kinases in murine fibroblasts [J].

Cheng, MG ;

Olivier, P ;

Diehl, JA ;

Fero, M ;

Roussel, MF ;

Roberts, JM ;

Sherr, CJ .

EMBO JOURNAL, 1999, 18 (06) :1571-1583

[5] A critical role for p27kip1 gene dosage in a mouse model of prostate carcinogenesis [J].

Gao, H ;

Ouyang, X ;

Banach-Petrosky, W ;

Borowsky, AD ;

Yong, L ;

Kim, M ;

Lee, H ;

Shih, WJ ;

Cardiff, RD ;

Shen, MM ;

Abate-Shen, C .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (49) :17204-17209

[6]

Hu GZ, 2001, DEVELOPMENT, V128, P2373

[7] Cdx1 inhibits the proliferation of human colon cancer cells by reducing cyclin D1 gene expression [J].

Lynch, J ;

Keller, M ;

Guo, RJ ;

Yang, D ;

Traber, P .

ONCOGENE, 2003, 22 (41) :6395-6407

[8] The caudal-related homeodomain protein Cdx1 inhibits proliferation of intestinal epithelial cells by down-regulation of D-type cyclins [J].

Lynch, J ;

Suh, ER ;

Silberg, DG ;

Rulyak, S ;

Blanchard, N ;

Traber, PG .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (06) :4499-4506

[9] Role of p27 in prostate carcinogenesis [J].

Macri, E ;

Loda, M .

CANCER AND METASTASIS REVIEWS, 1998, 17 (04) :337-344

[10] ErbB2/Neu-induced, cyclin D1-dependent transformation is accelerated in p27-haploinsufficient mammary epithelial cells but impaired in p27-null cells [J].

Muraoka, RS ;

Lenferink, AEG ;

Law, B ;

Hamilton, E ;

Brantley, DM ;

Roebuck, LR ;

Arteaga, CL .

MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (07) :2204-2219