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Gastrointestinal hyperplasia with altered expression of DNA polymerase β

Yoshizawa, K and Jelezcova, E and Brown, AR and Foley, JF and Nyska, A and Cui, X and Hofseth, LJ and Maronpot, RM and Wilson, SH and Sepulveda, AR and Sobol, RW (2009) Gastrointestinal hyperplasia with altered expression of DNA polymerase β. PLoS ONE, 4 (8).

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Abstract

Background: Altered expression of DNA polymerase β (Pol β) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol β over-expression has not yet been evaluated in a mouse model. Methodology/Principal Findings: We have recently developed a novel transgenic mouse model that over-expresses Pol β. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol β over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol β expression. We observed elevated expression of Pol β in stomach adenomas and thyroid follicular carcinomas, but reduced Pol β expression in esophageal adenocarcinomas and squamous carcinomas. Conclusions/Significance: These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Yoshizawa, K
Jelezcova, E
Brown, AR
Foley, JF
Nyska, A
Cui, X
Hofseth, LJ
Maronpot, RM
Wilson, SH
Sepulveda, AR
Sobol, RWrws9@pitt.eduRWS9
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHarris, Reuben S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Hillman Cancer Center
Other Centers, Institutes, Offices, or Units > Pittsburgh Cancer Institute
Date: 5 August 2009
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 4
Number: 8
DOI or Unique Handle: 10.1371/journal.pone.0006493
Schools and Programs: Graduate School of Public Health > Human Genetics
Refereed: Yes
MeSH Headings: Animals; DNA Polymerase beta--genetics; DNA Repair; Disease Models, Animal; Gastrointestinal Neoplasms--genetics; Gastrointestinal Tract--pathology; Hyperplasia; Mice; Mice, Transgenic; Reverse Transcriptase Polymerase Chain Reaction
PubMed Central ID: PMC2716528
PubMed ID: 19654874
Date Deposited: 03 Aug 2012 16:07
Last Modified: 02 Feb 2019 16:56
URI: http://d-scholarship.pitt.edu/id/eprint/13161

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