Gastrointestinal hyperplasia with altered expression of DNA polymerase beta.
BACKGROUND
Altered expression of DNA polymerase beta (Pol beta) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol beta over-expression has not yet been evaluated in a mouse model.


RESULTS
We have recently developed a novel transgenic mouse model that over-expresses Pol beta. 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 beta over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol beta expression. We observed elevated expression of Pol beta in stomach adenomas and thyroid follicular carcinomas, but reduced Pol beta expression in esophageal adenocarcinomas and squamous carcinomas.


CONCLUSIONS
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.
Yoshizawa
Katsuhiko
K
Cellular and Molecular Pathology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, United States of America.
Jelezcova
Elena
E
Brown
Ashley R
AR
Foley
Julie F
JF
Nyska
Abraham
A
Cui
Xiangli
X
Hofseth
Lorne J
LJ
Maronpot
Robert M
RM
Wilson
Samuel H
SH
Sepulveda
Antonia R
AR
Sobol
Robert W
RW
D000818:Animals; D019951:DNA Polymerase beta / Q000235:genetics*; D004260:DNA Repair; D004195:Disease Models, Animal; D005770:Gastrointestinal Neoplasms / Q000235:genetics*; D041981:Gastrointestinal Tract / Q000473:pathology*; D006965:Hyperplasia; D051379:Mice; D008822:Mice, Transgenic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019951:DNA Polymerase beta