The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas.

The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Research Abstract Details 

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The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Abstract Text:

Eva Hernando,Elizabeth Charytonowicz,Maria E Dudas,Silvia Menendez,Igor Matushansky,Joslyn Mills,Nicholas D Socci,Nille Behrendt,Li Ma,Robert G Maki,Pier Paolo Pandolfi,Carlos Cordon-Cardo,

We analyzed the PI3K-AKT signaling cascade in a cohort of sarcomas and found a marked induction of insulin receptor substrate-2 (IRS2) and phosphorylated AKT and a concomitant upregulation of downstream effectors in most leiomyosarcomas. To determine the role of aberrant PI3K-AKT signaling in leiomyosarcoma pathogenesis, we genetically inactivated Pten in the smooth muscle cell lineage by cross-breeding Pten(loxP/loxP) mice with Tagln-cre mice. Mice carrying homozygous deletion of Pten alleles developed widespread smooth muscle cell hyperplasia and abdominal leiomyosarcomas, with a very rapid onset and elevated incidence (approximately 80%) compared to other animal models. Constitutive mTOR activation was restricted to the leiomyosarcomas, revealing the requirement for additional molecular events besides Pten loss. The rapamycin derivative everolimus substantially decelerated tumor growth on Tagln-cre/Pten(loxP/loxP) mice and prolonged their lifespan. Our data show a new and critical role for the AKT-mTOR pathway in smooth muscle transformation and leiomyosarcoma genesis, and support treatment of selected sarcomas by the targeting of this pathway with new compounds or combinations of these with conventional chemotherapy agents.

The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Publishing Authors By Initials

E Hernando,E Charytonowicz,ME Dudas,S Menendez,I Matushansky,J Mills,ND Socci,N Behrendt,L Ma,RG Maki,PP Pandolfi,C Cordon-Cardo,

For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

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The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature medicine

VOLUME: 13

Page Numbers: 748-53

Journal Abbreviation: Nat. Med.

ISSN: 1078-8956

DAY: 13

MONTH: 05

YEAR: 2007

The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502015

The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Keywords Mesh Terms:

KEYWORDS: Signal Transduction

MESH TERMS: physiology

Chemical & Substance for Abstract: The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Information

Substance Name: PTEN Phosphohydrolase

Registry Number: EC 3.1.3.67

Grant and Affiliation Information for The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas.

AFFILIATION: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.

Country: United States

AGENCY: United States NCI

GRANT: P01 CA47179

ACRONYM: CA

MEDLINETA: Nat Med

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