期刊
GENES & DEVELOPMENT
卷 19, 期 15, 页码 1773-1778出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.1314605
关键词
Cowden disease; FOXO; PKB; forkhead; hamartoma syndromes; tuberous sclerosis complex
资金
- NCI NIH HHS [P01 CA089021, CA89021] Funding Source: Medline
- NIGMS NIH HHS [R01 GM041890] Funding Source: Medline
- NINDS NIH HHS [R01 NS031535, R37 NS031535, NS31535] Funding Source: Medline
The PTEN and TSC2 tumor suppressors inhibit mammalian target of rapamycin (mTOR) signaling and are defective in distinct hamartoma syndromes. Using mouse genetics, we find that Pten and Tsc2 act synergistically to suppress the severity of a subset of tumors specific to loss of each of these genes. Interestingly, we find that the slow-growing tumors specific to Tsc2(+/-) mice exhibit defects in signaling downstream of Akt. However, Pten haploinsufficiency restores Akt signaling in these tumors and dramatically enhances their severity. This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature.
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