Aberrant activation of mammalian target of rapamycin complex 1 (mTORC1), caused 
by loss or inactivation of TSC1/TSC2 protein complex, leads to negative feedback 
inhibition of Akt. The exact mechanisms of this process are still not fully 
understood. Here we present evidence for the involvement of STAT3, a known 
mTORC1 regulated transcription factor, in this process. We demonstrate that 
STAT3 promotes the transcription of PTEN by directly binding on the PTEN 
promoter. Elevated PTEN then inhibits the proliferation of Tsc1(-/-) or 
Tsc2(-/-) cells through down-regulation of Akt signaling. Activation of PTEN in 
this pathway may thus serve as a protective mechanism against hyper-activated 
mTORC1 mediated tumorigenesis and contribute to the benign nature of tumors 
caused by loss of either TSC1 or TSC2.