dc.creator | Mogal, Ashish Popatrao | |
dc.date.accessioned | 2020-08-22T17:09:26Z | |
dc.date.available | 2008-06-21 | |
dc.date.issued | 2007-06-21 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-06212007-085438 | |
dc.identifier.uri | http://hdl.handle.net/1803/12650 | |
dc.description.abstract | This project is focused on understanding the molecular mechanisms of prostate tumor initiation due the loss of the tumor suppressor gene Nkx3.1. Here, we examined the dosage-sensitive and stochastic target gene regulation by Nkx3.1 as a mechanism of haploinsufficient prostate tumor suppression. Our results showed that the dosage-sensitive and insensitive Nkx3.1 target genes are regulated by differential H3/H4 acetylation and Nkx3.1 occupancy in vivo. Our findings underscore the importance of chromatin accessibility in dosage-sensitive target gene regulation by Nkx3.1. We next established the functional significance of dosage-sensitive Nkx3.1 target gene intelectin / omentin in prostate tumorigenesis. We found that intelectin suppresses prostate cell growth in vitro and in vivo suggesting its tumor suppressor-like activity in prostate cancer. In summary, our results provide an example of how a genetic lesion such as haploid loss of the Nkx3.1 tumor suppressor can engender epigenetic changes such as alterations in histone H3/H4 acetylation that selectively inactivate a dosage-sensitive target gene important for suppressing tumorigenicity. | |
dc.format.mimetype | application/pdf | |
dc.subject | Histone acetylation | |
dc.subject | Gene expression | |
dc.subject | Nkx3.1 | |
dc.subject | Prostate cancer | |
dc.subject | Chromatin | |
dc.subject | Dosage | |
dc.subject | Homeobox genes | |
dc.subject | Prostate -- Cancer -- Genetic aspects | |
dc.title | Analysis of Nkx3.1 Target Genes in Prostate Cancer | |
dc.type | dissertation | |
dc.contributor.committeeMember | Dr. Simon Hayward | |
dc.contributor.committeeMember | Dr. David Head | |
dc.contributor.committeeMember | Dr. Zu-Wen Sun | |
dc.contributor.committeeMember | Dr. Pampee Young | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Pathology | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2008-06-21 | |
local.embargo.lift | 2008-06-21 | |
dc.contributor.committeeChair | Dr. Fritz Parl | |