Pdx-1-driven overexpression of aurora a kinase induces mild ductal dysplasia of pancreatic ducts near islets in transgenic mice.
OBJECTIVE
To further explore the oncogenic activity of Aurora A kinase while attempting to develop a useful mouse model for pancreatic cancer, Aurora A kinase was targeted to pancreatic duodenal homeobox gene-1 (Pdx-1)-positive cells.


METHODS
Aurora A kinase overexpression was targeted to mouse pancreas tissues using the Pdx-1 promoter in a transgenic model. The pancreas tissues of 7- to 11-month-old transgenic animals were evaluated for metastatic adenocarcinomas, preinvasive ductal neoplasia, or other histological anomalies.


RESULTS
Examination of pancreatic tissue from Pdx-1-Aurora A transgenic mice revealed abnormalities, such as mild islet cell hyperplasia, lymphocytic infiltration, and general dysplasia between ductal/islet cell interfaces. However, most tissues from these transgenic mice were normal.


CONCLUSIONS
The overexpression of Aurora A can potentially initiate the development of mild abnormalities in pancreatic tissue; however, neither preinvasive ductal neoplasia nor fully metastatic adenocarcinomas were observed. Combining the Pdx-1-Aurora A transgenic model with other genetic alterations may provide additional insight.
Warner
Steven L
SL
College of Pharmacy, University of Arizona, Tucson, AZ, USA.
Muñoz
Ruben M
RM
Bearss
David J
DJ
Grippo
Paul
P
Han
Haiyong
H
Von Hoff
Daniel D
DD
D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006965:Hyperplasia; D007515:Islets of Langerhans / Q000201:enzymology* / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010183:Pancreatic Ducts / Q000201:enzymology* / Q000473:pathology; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics*
D018398:Homeodomain Proteins; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases