The zinc finger protein GLI induces cellular sensitivity to the mTOR inhibitor rapamycin.

摘要: The protein synthetic machinery is activated by diverse genetic alterations during tumor progression in vivo and represents an attractive target for cancer therapy. We show that rapamycin inhibits the induction of transformed foci vitro GLI, a transcription factor functions sonic hedgehog-patched pathway tumors. In control cells, which were nontransformed epithelioid RK3E cells derivative c-MYC- or RAS-transformed sister cell lines, mTOR mTOR-dependent activities but increases global synthesis, perhaps activating feedback mechanism. GLI-transformed synthesis turnover prevents cellular proliferation. contrast to its effects on affects bromodeoxyuridine incorporation cycle occupancy GLI similar extent. Rare, variant isolated selection are also drug-resistant metabolism through G1. Our results indicate sensitivity can be induced specific oncogene inhibition linked rapamycin-sensitive phenotype.