Director:
Chi Dang, M.D., Ph.D. (PI)
Brief Discription and findings:
We obtained from Dr. Dean Felsher (Stanford Univ.) a tetracycline-inducible Myc model of hepatocellular carcinoma (HCC). In this system, a significant number of adult mice devoid of doxycycline develop HCC within several months. PET FDG studies with engineered or treated mice (see below) showed significant differences in FDG uptake. The use of an inducible system allowed us to assess changes in glucose uptake with time. In a parallel cohort of induced Myc mice, we assessed changes in hepatic gene expression with time and correlated this with changes in glucose uptake. We also obtained from Dr. Fred Alt (Harvard Univ.) mice that contain floxed Myc alleles. We successfully performed tail vein injections with Cre recombinase expressing adenovirus to delete Myc from hepatocytes. We plan to determine the function of endogenous Myc in glucose uptake via PET. In part through using these mice, we have discovered that Myc induces mitochondrial biogenesis. More recently, we have established the direct induction of the majority of glycolytic genes by Myc. Gene profiling along with imaging are providing additional insights into time-dependent processes of Myc-induced tumorigenesis.
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