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Characterization of Cellular and Genomic Effects of 1,25-Dihydroxyvitamin D3 in Prostate Progenitor/Stem Cells

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title
Characterization of Cellular and Genomic Effects of 1,25-Dihydroxyvitamin D3 in Prostate Progenitor/Stem Cells
author
Maund, Sophia Lisette
abstract
Prostate cancer is the most frequently-occurring non-cutaneous cancer and the second-deadliest cancer in American men. Early-stage prostate cancer can be eradicated by surgery or radiation with a 100% 5-year survival rate. Late-stage prostate cancer is treated with hormone ablation therapy, but the 5-year survival rate drops to ~40% due to metastatic spread and/or development of androgen-independent prostate cancer. Even men whose prostate cancer is detected and treated at early stages can experience side effects that negatively impact quality of life. Prostate cancer develops over the course of decades, so there is opportunity for prevention. Epidemiologic and laboratory studies support the potential for vitamin D3 as a chemopreventative agent for prostate cancer. The prostate cancer stem cell hypothesis, which is still under development, proposes that a transformed adult prostate progenitor/stem cell can give rise to a heterogeneous prostate tumor. Based on this hypothesis, we posit that the prostate progenitor/stem cell is the most relevant target for chemoprevention. We investigate herein the cellular and genomic effects of 1,25 dihydroxyvitamin D3 (the metabolically active form of vitamin D3) on the prostate progenitor/stem cell and discuss their implications for prostate cancer chemoprevention. We used genomic microarrays to analyze the transcriptional profiles of prostate progenitor/stem cells in response to 1,25 dihydroxyvitamin D3 and systems, molecular, and cellular biology techniques to reveal a role for the cytokine interleukin-1 alpha (IL1 alpha) as a novel signaling target in the prostate progenitor/stem cell response to 1,25 dihydroxyvitamin D3. IL1 alpha is a common target in the 1,25 dihydroxyvitamin D3 response, as evidenced by its newfound role in mammary epithelial cells as well. This work supports the use of vitamin D3 as a chemopreventative agent and it presents a model for elucidating its mechanisms of action.
subject
Chemoprevention
Interleukin 1 alpha
Prostate
Stem cell
Vitamin D
contributor
Cramer, Scott D (committee chair)
Sui, Guangchao (committee member)
Kridel, Steven (committee member)
Chen, Yong (committee member)
date
2011-07-14T20:35:23Z (accessioned)
2011 (issued)
degree
Cancer Biology (discipline)
identifier
http://hdl.handle.net/10339/33443 (uri)
language
en (iso)
publisher
Wake Forest University
type
Dissertation

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