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Dissertation
Transforming growth factor beta and oncogenes c-myc and Bmi-1 contribute to the malignant transformation of intermediary basal epithelial cells of the prostate
Doctor of Philosophy (Ph.D.), Drexel University
Sep 2009
DOI:
https://doi.org/10.17918/00000809
Abstract
Unraveling the etiology of prostate cancer development requires a crucial understanding of the factors controlling normal prostate growth and development. Isaacs and Coffey postulated that the basal layer consist of a stem-like cell that is the progenitor of all epithelial cell types in the prostate. It is now known that differentiating transit-amplifying cells give rise to heterogenous cell populations which migrate into the luminal layer from the basal layer (i.e. intermediate basal cells or IBCs), but there is limited data on the changing epithelial cell phenotypes during differentiation. The work presented here characterized intermediary basal cells isolated and cultured in our lab. In Chapter 2, we examined the CD133+ TIC sub-population and demonstrated a requirement of c-myc for both anchorage-independent growth in vitro and in vivo. In Chapter 4, we examined the TGF[beta] pathway ability to regulate the VEGFR3 signaling axis. Our results demonstrated that TGF[beta]-mediated disruption of cell-cell junction promoted membrane surface of VEGFR3, and together the two pathways functioned in synergy to promote cell migration and invasion. In Chapter 5 we examined the impact altered Bmi-1 expression has on the induction of an EMT phenotype and subsequent cell migration. We found that Bmi-1 expression is required for the acquisition of an EMT phenotype and that forced expression of Bmi-1 greatly increases the invasive capacity of the intermediary basal cells examined here. All together, the work presented here demonstrate that IBCs provide a suitable model to examine molecular pathways that contribute to prostate tumorigenesis, and further characterization of the properties of IBCs will advance our understanding of changes in cell phenotype associated with the transitions towards malignancy.
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Details
- Title
- Transforming growth factor beta and oncogenes c-myc and Bmi-1 contribute to the malignant transformation of intermediary basal epithelial cells of the prostate
- Creators
- Shaun Michael Goodyear
- Contributors
- Mark E. Stearns (Advisor)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 171 pages, 2 unnumbered pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 991014970186704721