期刊
SCIENCE SIGNALING
卷 2, 期 55, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.2000189
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资金
- NCI NIH HHS [R01 CA082328-12, U01 CA084292-10, U01 CA084292, R24CA83084, R01 CA082328-07, U24 CA083084-10, R01 CA082328-06, R01 CA082328-05, P30 CA008748, U01 CA-84292, R01 CA-82328, P30 CA08748, R24 CA083084, U24 CA083084, R01 CA082328, U01 CA084292-06, U01 CA084292-07, U01 CA084292-08] Funding Source: Medline
- NIMHD NIH HHS [R01 MD004038] Funding Source: Medline
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.
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