Requirement for Interaction of PI3-Kinase p110α with RAS in Lung Tumor Maintenance

被引：140

作者：

Castellano, Esther ^{[1
]}

Sheridan, Clare ^{[1
]}

Thin, May Zaw ^{[2
]}

Nye, Emma ^{[3
]}

Spencer-Dene, Bradley ^{[3
]}

Diefenbacher, Markus E. ^{[4
]}

Moore, Christopher ^{[1
]}

Kumar, Madhu S. ^{[1
]}

Murillo, Miguel M. ^{[1
,6
]}

Groenroos, Eva ^{[5
]}

Lassailly, Francois ^{[2
]}

Stamp, Gordon ^{[3
]}

Downward, Julian ^{[1
,6
]}

机构：

[1] Canc Res UK London Res Inst, Signal Transduct Lab, London WC2A 3LY, England

[2] Canc Res UK London Res Inst, In Vivo Imaging Facil, London WC2A 3LY, England

[3] Canc Res UK London Res Inst, Expt Histopathol Lab, London WC2A 3LY, England

[4] Canc Res UK London Res Inst, Mammalian Genet Lab, London WC2A 3LY, England

[5] Canc Res UK London Res Inst, Translat Canc Therapeut Lab, London WC2A 3LY, England

[6] Inst Canc Res, Div Canc Biol, Lung Canc Grp, London SW3 6JB, England

来源：

CANCER CELL | 2013年 / 24卷 / 05期

关键词：

K-RAS; SIGNALING PATHWAYS; ACTIVATION; CANCER; TUMORIGENESIS; 3-KINASE; GROWTH; PI3K; KRAS; CHEMOTHERAPY;

D O I：

10.1016/j.ccr.2013.09.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

RAS proteins directly activate PI3-kinases. Mice bearing a germline mutation in the RAS binding domain of the p110 alpha subunit of PI3-kinse are resistant to the development of RAS-driven tumors. However, it is unknown whether interaction of RAS with PI3-kinase is required in established tumors. The need for RAS interaction with p110 alpha in the maintenance of mutant Kras-driven lung tumors was explored using an inducible mouse model. In established tumors, removal of the ability of p110 alpha to interact with RAS causes long-term tumor stasis and partial regression. This is a tumor cell-autonomous effect, which is improved significantly by combination with MEK inhibition. Total removal of p110 alpha expression or activity has comparable effects, albeit with greater toxicities.

引用

页码：617 / 630

页数：14

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