Synergistic Action of FOXP3 and TSC1 Pathways During Tumor Progression
Annual rept. 29 Sep 2014-28 Sep 2015
ALABAMA UNIV IN BIRMINGHAM
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Foxp3, the first identified X-linked prostate tumor suppressor, represses c-Myc in both the mouse and human prostate. Dysfunction of the Foxp3-c-Myc axis may lead to prostate cancer initiation. Tsc1 and Foxp3 double-deletions in the mouse prostate led to prostate carcinoma at an early age. In this proposed study, we observed that deletion of Tsc1 led to a constitutive mTOR activation and subsequently increases phosphorylation of c-Myc at threonine 58 pT58 and decreases phosphorylation at serine 62 pS62. Furthermore, loss of Foxp3 transcriptionally induces c-Myc expression and loss of Tsc1 activates mTOR signaling, leading a cross-talk between Foxp3-c-Myc and Tsc1-mTOR signaling pathways that converges on c-Myc and promoted tumor progression. This observation will help us understand how double Foxp3 and Tsc1 deficiencies promote tumor progression of prostate cancer.
- Medicine and Medical Research