Somatic Mutations in p85α Promote Tumorigenesis through Class IA PI3K Activation

被引：255

作者：

Jaiswal, Bijay S. ^{[1
]}

Janakiraman, Vasantharajan ^{[1
]}

Kljavin, Noelyn M. ^{[1
]}

Chaudhuri, Subhra ^{[1
]}

Stern, Howard M. ^{[2
]}

Wang, Weiru ^{[3
]}

Kan, Zhengyan ^{[1
]}

Dbouk, Hashem A. ^{[7
]}

Peters, Brock A. ^{[1
]}

Waring, Paul ^{[2
]}

Dela Vega, Trisha ^{[3
]}

Kenski, Denise M. ^{[1
]}

Bowman, Krista K. ^{[3
]}

Lorenzo, Maria ^{[4
]}

Li, Hong ^{[4
]}

Wu, Jiansheng ^{[4
]}

Modrusan, Zora ^{[1
]}

Stinson, Jeremy ^{[1
]}

Eby, Michael ^{[5
]}

Yue, Peng ^{[6
]}

Kaminker, Josh S. ^{[6
]}

de Sauvage, Frederic J. ^{[1
]}

Backer, Jonathan M. ^{[7
]}

Seshagiri, Somasekar ^{[1
]}

机构：

[1] Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA

[2] Genentech Inc, Dept Pathol, San Francisco, CA 94080 USA

[3] Genentech Inc, Dept Prot Engn, San Francisco, CA 94080 USA

[4] Genentech Inc, Dept Prot Chem, San Francisco, CA 94080 USA

[5] Genentech Inc, Dept Translat Oncol, San Francisco, CA 94080 USA

[6] Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA

[7] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA

来源：

CANCER CELL | 2009年 / 16卷 / 06期

基金：

美国国家卫生研究院;

关键词：

P85 REGULATORY SUBUNIT; 3-KINASE CATALYTIC SUBUNIT; PHOSPHOINOSITIDE; 3-KINASE; PHOSPHATIDYLINOSITOL; PIK3CA MUTATIONS; GLIOBLASTOMA-MULTIFORME; FUNCTIONAL-ANALYSIS; COLORECTAL-CANCER; TYROSINE KINASES; GENE;

D O I：

10.1016/j.ccr.2009.10.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Members of the mammalian phosphoinositide-3-OH kinase (PI3K) family of proteins are critical regulators of various cellular process including cell survival, growth, proliferation, and motility. Oncogenic activating mutations in the p110 alpha catalytic subunit of the heterodimeric p110/p85 PI3K enzyme are frequent in human cancers. Here we show the presence of frequent mutations in p85 alpha in colon cancer, a majority of which occurs in the inter-Src homology-2 (iSH2) domain. These mutations uncouple and retain p85 alpha's p110-stabilizing activity, while abrogating its p110-inhibitory activity. The p85 alpha mutants promote cell survival, AKT activation, anchorage-independent cell growth, and oncogenesis in a p110-dependent manner.

引用

页码：463 / 474

页数：12

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