Effects of HBP1 Overexpression and EGCG/DAC Treatment on Growth and Metabolism in Triple-Negative Breast Cancer.
Pedro, Brian.
2014
- Abstract: The protein HBP1, a transcriptional repressor known to regulate Wnt signaling by preventing expression of Wnt target genes, has been found to be deleted or mutated in clinical invasive breast cancer samples, especially in triple-negative cancers which have increased Wnt signaling. Additionally, decreases in HBP1 have been associated with a shift in carbon metabolism, termed the Warburg ... read moreeffect, which is commonly found in cancer cells. Therefore, we hypothesized that in addition to regulating Wnt signaling, changes in HBP1 levels may also be responsible for the altered carbon metabolism exhibited by cancer cells. Using MDA-MB-231 cells, a human triple-negative breast cancer (TNBC) line, we examined the biochemical effects of HBP1 overexpression through both in vitro and in vivo experiments. Then, we performed further in vivo experiments using IS13 TNBC cells, in which we examined the efficacy of EGCG/Decitabine (DAC) treatment, a method known to induce HBP1. In both cases, in vivo experiments were performed by orthotopically implanting NOD/SCID mice with TNBC cells. We hypothesized that both HBP1 overexpression and EGCG/DAC treatment would result in reduction of Wnt signaling and Warburg effect enzymes in the treated tumors. The Western blot and qRT-PCR data for both experiments, along with 1H-NMR data for the EGCG/DAC experiments, indicate that both HBP1 overexpression and EGCG/DAC treatment result in metabolic shifts away from the Warburg effect, and that EGCG/DAC can directly suppress growth of TNBC tumors.read less
- ID:
- 2v23w5415
- Component ID:
- tufts:sd.0000025
- To Cite:
- TARC Citation Guide EndNote
