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Master of Science (MS)
Molecular and Cellular Pharmacology (Medicine)
Date of Defense
First Committee Member
Gennaro D'Urso - Committee Chair
Second Committee Member
Diane M. Lopez, Ph.D - Committee Member
Third Committee Member
Michael D. Kim - Committee Member
Fourth Committee Member
Keith A.Webster - Mentor
Prostate cancer is the second most common cancer among men in the United States. While treatments for prostate cancer exist, none are curative. As a solid tumor, prostate cancer can grow beyond the diffusion limits of oxygen, thereby resulting in a hypoxic environment. While hypoxia can cause death to a variety of cell types, tumor cells can develop resistance to hypoxia and survive under minimal oxygen conditions. Hypoxia in tumor cells has also been associated with poor prognosis, increased metastasis, and decreased efficacy of chemotherapy. BNIP3, a BH-3 only proapoptotic Bcl-2 family member, has been shown to play an important role in cell death under hypoxic conditions in a variety of cell types. In normoxia, BNIP3 shows little to no expression in both cardiomyocytes and many cancer cell types, but is then upregulated under hypoxic conditions. Previous work in our laboratory provides evidence that hypoxia alone, as well as the concomitant increase in BNIP3 expression, cannot cause death of rat neonatal cardiomyocytes. Instead, our studies found that hypoxia with concomitant intracellular acidosis is required. Further studies indicated that BNIP3 is also necessary for hypoxia-acidosis associated cell death in cardiomyocytes. Our results in rat neonatal cardiomyocytes led us to hypothesize that cell death could be induced in hypoxic prostate cancer cells if concomitant acidosis could be induced. Additionally, our intention was to determine if BNIP3 was required for any prostate cancer cell death that may occur under hypoxia-acidosis conditions.
DNA Fragmentation; Apoptosis; V-ATPase; NHE; HIF; BNIP3; Bcl-2 Family; PH
Faysal, Joanne M., "The Effects of Hypoxia with Concomitant Acidosis on Prostate Cancer Cell Survival" (2010). Open Access Theses. 69.