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  • Differential requirement of mTOR in postmitotic tissues and tumorigenesis.

Differential requirement of mTOR in postmitotic tissues and tumorigenesis.

Science signaling (2009-01-30)
Caterina Nardella, Arkaitz Carracedo, Andrea Alimonti, Robin M Hobbs, John G Clohessy, Zhenbang Chen, Ainara Egia, Alessandro Fornari, Michelangelo Fiorentino, Massimo Loda, Sara C Kozma, George Thomas, Carlos Cordon-Cardo, Pier Paolo Pandolfi
ABSTRACT

The mammalian target of rapamycin (mTOR) is a crucial effector in a complex signaling network commonly disrupted in cancer. mTOR exerts its multiple functions in the context of two different multiprotein complexes: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Loss of the tumor suppressor PTEN (phosphatase and tensin homolog deleted from chromosome 10) can hyperactivate mTOR through AKT and represents one of the most frequent events in human prostate cancer. We show here that conditional inactivation of mTor in the adult mouse prostate is seemingly inconsequential for this postmitotic tissue. Conversely, inactivation of mTor leads to a marked suppression of Pten loss-induced tumor initiation and progression in the prostate. This suppression is more pronounced than that elicited by the sole pharmacological abrogation of mTORC1. Acute inactivation of mTor in vitro also highlights the differential requirement of mTor function in proliferating and transformed cells. Collectively, our data constitute a strong rationale for developing specific mTOR inhibitors targeting both mTORC1 and mTORC2 for the treatment of tumors triggered by PTEN deficiency and aberrant mTOR signaling.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Formalin solution, neutral buffered, 10%, histological tissue fixative
Sigma-Aldrich
Formalin solution, neutral buffered, 10%, histological tissue fixative
Sigma-Aldrich
Formalin solution, neutral buffered, 10%, case of 24 × 60 mL, histological tissue fixative
Sigma-Aldrich
Formalin solution, neutral buffered, 10%, histological tissue fixative
Sigma-Aldrich
Formalin solution, neutral buffered, 10%, case of 48 × 15 mL, histological tissue fixative
Sigma-Aldrich
Formalin solution, neutral buffered, 10%, case of 24 × 120 mL, histological tissue fixative
Sigma-Aldrich
Formalin solution, neutral buffered, 10%, histological tissue fixative