A mouse model for cyclin E-dependent genetic instability and tumorigenesis

被引：95

作者：

Loeb, KR

Kostner, H

Firpo, E

Norwood, T

Tsuchiya, KD

Clurman, BE ^{[1
]}

Roberts, JM

机构：

[1] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98029 USA

[2] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98029 USA

[3] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98029 USA

[4] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98109 USA

[5] Univ Washington, Sch Med, Dept Med, Dept Biochem, Seattle, WA 98109 USA

[6] Childrens Hosp & Med Ctr, Howard Hughes Med Inst, Seattle, WA 98105 USA

[7] Childrens Hosp & Med Ctr, Dept Lab Med, Seattle, WA 98105 USA

来源：

CANCER CELL | 2005年 / 8卷 / 01期

关键词：

D O I：

10.1016/j.ccr.2005.06.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ubiquitination of murine cyclin E is triggered by phosphorylation on threonine 393. Cyclin ET393A knockin mice exhibited increased cyclin E stability, but no phenotypic abnormalities. Importantly, loss of the p53 pathway exacerbated the effect of the T393A mutation. Thus, in p21(-/-) cells the T393A mutation had an exaggerated effect on cyclin E abundance and its associated kinase activity, which caused abnormal cell cycle progression, and genetic instability involving chromosome breaks and translocations. Moreover, cyclin ET393A acted synergistically with p53 deficiency to accelerate tumorigenesis in cyclin ET393A p53(-/-) mice; Ras more readily transformed cyclin ET393A p53(-/-) cells than p53(-/-) cells in vitro; and cyclin ET393A mice had a greatly increased susceptibility to Ras-induced lung cancer.

引用

页码：35 / 47

页数：13

共 49 条

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