Mechanisms of Reactive Stroma-Induced Tumorigenesis in Prostate Cancer
Technical Report,01 Sep 2012,31 Aug 2016
Baylor College of Medicine Houston United States
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This project addressed the role of RUNX1 and ID1 transcription factors in regulating the biology of myofibroblast progenitor cells in the tumor microenvironment of prostate cancer. Task 1 used novel 3D organoid and co-culture models. We have found that RUNX1 is critical mediator of TGF-beta action in mesenchymal stemprogenitor cells. RUNX1 is critical for cell cycle progression and proliferation of progenitors. RUNX1 also limits differentiation tomyofibroblasts and maintains proliferative status. TGF-beta mediated gene expression and the role of RUNX1 have been determined. Experiments to address ID1 were changed in year 2-3 to address p53 in the NCE period. RUNX1 and p53 were found to regulate cell proliferation but not to interact. Importantly, we also found that IL-1apha regulated cell differentiation. Task 2 focused on in vivo biology and the role of the ELF3 factor. RUNX1 knockdown appeared to limit proliferation of myofibroblasts in xenograft tumors. ELF3 was found to mediate IL-1alpha induction to an immune reactive phenotype. Together, these studies point to critical roles of RUNX1 and ELF3 in the genesis of tumor-promoting reactive stroma in prostate cancer.
- Medicine and Medical Research
- Anatomy and Physiology