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- W2332635545 abstract "Abstract #6030 mTOR (mammalian target of rapamycin) signaling is a central regulator of cell growth and proliferation. Rapamycin and its analogues have been shown to inhibit breast cancer cell growth in preclinical models, and are actively being pursued in clinical trials. We performed a high-throughput microarray polysome analysis to identify novel genes whose expression was regulated by rapamycin at the level of transcription or translation. In three breast cancer cell lines representing different breast cancer subtypes, we found a significant decline in polysome-associated mRNA for stearoyl-CoA desaturase 1 (SCD1), the rate-limiting enzyme in monounsaturated fatty acid synthesis. Insulin and insulin-like growth factor, both activators of mTOR, increase SCD1 expression. Rapamycin and PI3K inhibitors decrease SCD1 protein, as does mTOR siRNA. Quantitative RT-PCR of total, polysomal and monosomal RNA, northern analysis and stability studies demonstrate that rapamycin regulates SCD1 at the level of transcription. Furthermore, rapamycin inhibits the SCD1 promoter activation by mevinolin, an inhibitor of cholesterol biosynthesis. We demonstrate that mTOR regulates SCD1 expression. This establishes a novel link between cell signaling and cancer cell fat metabolism. In doing so, we also present SCD1 as a potential marker of response to treatment by mTOR inhibitors. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6030." @default.
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- W2332635545 date "2009-01-15" @default.
- W2332635545 modified "2023-09-28" @default.
- W2332635545 title "mTOR modulates cellular fat metabolism by regulating stearoyl-CoA desaturase 1 transcription." @default.
- W2332635545 doi "https://doi.org/10.1158/0008-5472.sabcs-6030" @default.
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