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Title page for ETD etd-06212007-085438

Type of Document Dissertation
Author Mogal, Ashish Popatrao
Author's Email Address ashishmogal@yahoo.com
URN etd-06212007-085438
Title Analysis of Nkx3.1 Target Genes in Prostate Cancer
Degree PhD
Department Pathology
Advisory Committee
Advisor Name Title
Dr. Fritz Parl Committee Chair
Dr. David Head Committee Member
Dr. Pampee Young Committee Member
Dr. Simon Hayward Committee Member
Dr. Zu-Wen Sun Committee Member
  • Histone acetylation
  • Gene expression
  • Nkx3.1
  • Prostate cancer
  • Chromatin
  • Dosage
  • Homeobox genes
  • Prostate -- Cancer -- Genetic aspects
Date of Defense 2007-06-18
Availability unrestricted
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.

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