Mechanisms of Reactive Stroma-Induced Tumorigenesis in Prostate Cancer
Abstract
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 stem/progenitor 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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2016
- Accession Number
- AD1035701
Entities
People
- David R. Rowley
Organizations
- Baylor College of Medicine