Accession Number : AD1035701


Title :   Mechanisms of Reactive Stroma-Induced Tumorigenesis in Prostate Cancer


Descriptive Note : Technical Report,01 Sep 2012,31 Aug 2016


Corporate Author : Baylor College of Medicine Houston United States


Personal Author(s) : Rowley,David R


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/1035701.pdf


Report Date : 01 Nov 2016


Pagination or Media Count : 21


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.


Descriptors :   transcription factors , prostate cancer , stromal cells


Subject Categories : Medicine and Medical Research
      Anatomy and Physiology


Distribution Statement : APPROVED FOR PUBLIC RELEASE