Senescence-Associated Oxidative DNA Damage Promotes the Generation of Neoplastic Cells

被引：81

作者：

Gosselin, Karo ^{[1
,2
,3
,4
,5
]}

Martien, Sebastien ^{[1
,2
,3
,4
,5
]}

Pourtier, Albin ^{[1
,2
,3
,4
,5
]}

Vercamer, Chantal ^{[1
,2
,3
,4
,5
]}

Ostoich, Peter ^{[7
]}

Morat, Luc ^{[7
]}

Sabatier, Laure ^{[7
]}

Duprez, Laurence ^{[8
]}

de Roodenbeke, Claire T'Fint ^{[9
]}

Gilson, Eric ^{[9
]}

Malaquin, Nicolas ^{[1
,2
,3
,4
,5
]}

Wernert, Nicolas ^{[10
]}

Slijepcevic, Predrag ^{[11
]}

Ashtari, Marjan ^{[11
]}

Chelli, Fazia ^{[1
,2
,3
,4
,5
]}

Deruy, Emeric ^{[1
,2
,3
,4
,5
]}

Vandenbunder, Bernard ^{[1
,3
,6
]}

De Launoit, Yvan ^{[1
,2
,3
,4
,5
]}

Abbadie, Corinne ^{[1
,2
,3
,4
,5
]}

机构：

[1] Univ Lille Nord France, Lille, France

[2] CNRS, UMR8161, Lille, France

[3] UDSL, Lille, France

[4] Inst Pasteur, F-59019 Lille, France

[5] USTI, Villeneuve Dascq, France

[6] CNRS, UMR3078, Villeneuve Dascq, France

[7] CEA, Div Life Sci, Fontenay Aux Roses, France

[8] Erasme ULB CHU Brugmann, Lab Cytogenet, Brussels, Belgium

[9] Univ Lyon 1, Fac Med Lyon Sud, CNRS, UMR5239, Pierre Benite, France

[10] Univ Bonn, Inst Pathol, D-5300 Bonn, Germany

[11] Brunel Univ, Brunel Inst Canc Genet & Pharmacogenom, Uxbridge UB8 3PH, Middx, England

来源：

CANCER RESEARCH | 2009年 / 69卷 / 20期

关键词：

MAMMARY EPITHELIAL-CELLS; IN-VIVO; REPLICATIVE SENESCENCE; CELLULAR SENESCENCE; TELOMERE LOSS; KERATINOCYTES; FIBROBLASTS; CULTURE; IMMORTALIZATION; TRANSFORMATION;

D O I：

10.1158/0008-5472.CAN-08-2510

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Studies on human fibroblasts have led to viewing senescence as a barrier against tumorigenesis. Using keratinocytes, we show here that partially transformed and tumorigenic cells systematically and spontaneously emerge from senescent cultures. We show that these emerging cells are generated from senescent cells, which are still competent for replication, by an unusual budding-mitosis mechanism. We further present data implicating reactive oxygen species that accumulate during senescence as a potential mutagenic motor of this post-senescence emergence. We conclude that senescence and its associated oxidative stress could be a tumor-promoting state for epithelial cells, potentially explaining why the incidence of carcinogenesis dramatically increases with advanced age. [Cancer Res 2009;69(20):7917-25]

引用

页码：7917 / 7925

页数：9

共 39 条

[1] N-t-butyl hydroxylamine, a hydrolysis product of α-phenyl-N-t-butyl nitrone, is more potent in delaying senescence in human lung fibroblasts [J].