DJ-1, a novel regulator of the tumor suppressor PTEN

被引：480

作者：

Kim, RH

Peters, M

Jang, YJ

Shi, W

Pintilie, M

Fletcher, GC

DeLuca, C

Liepa, J

Zhou, L

Snow, B

Binari, RC

Manoukian, AS

Bray, MR

Liu, FF

Tsao, MS

Mak, TW ^{[1
]}

机构：

[1] Adv Med Discovery Inst, Campbell Family Inst Breast Canc Res, Ontario Canc Inst, Toronto, ON M5G 2C1, Canada

[2] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2C1, Canada

[3] Princess Margaret Hosp, Dept Clin Informat, Toronto, ON M5G 2M9, Canada

[4] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M5G 2M9, Canada

[5] Princess Margaret Hosp, Dept Lab Med & Pathobiol, Toronto, ON M5G 2M9, Canada

[6] Miikana Therapeut Inc, Toronto, ON M5G 2C1, Canada

来源：

CANCER CELL | 2005年 / 7卷 / 03期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1016/j.ccr.2005.02.010

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The phosphatidylinositol 3' kinase (P13'K) pathway, which regulates cell survival, is antagonized by the PTEN tumor suppressor. The regulation of PTEN is unclear. A genetic screen of Drosophila gain-of-function mutants identified DJ-1 as a suppressor of PTEN function. In mammalian cells, DJ-1 underexpression results in decreased phosphorylation of PKB/ Akt, while DJ-1 overexpression leads to hyperphosphorylation of PKB/Akt and increased cell survival. In primary breast cancer samples, DJ-1 expression correlates negatively with PTEN immunoreactivity and positively with PKB/Akt hyperphosphorylation. In 19/23 primary non-small cell lung carcinoma samples, DJ-1 expression was increased compared to paired nonneoplastic lung tissue, and correlated positively with relapse incidence. DJ-1 is thus a key negative regulator of PTEN that may be a useful prognostic marker for cancer.

引用

页码：263 / 273

页数：11

共 73 条

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