Pdx-1-driven overexpression of aurora a kinase induces mild ductal dysplasia of pancreatic ducts near islets in transgenic mice

Pancreas. 2008 Oct;37(3):e39-44. doi: 10.1097/MPA.0b013e318176b9ae.

Abstract

Objectives: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aurora Kinase A
  • Aurora Kinases
  • Homeodomain Proteins / genetics*
  • Humans
  • Hyperplasia
  • Islets of Langerhans / enzymology*
  • Islets of Langerhans / pathology
  • Lymphocytes / pathology
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Pancreatic Ducts / enzymology*
  • Pancreatic Ducts / pathology
  • Promoter Regions, Genetic*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Trans-Activators / genetics*

Substances

  • Homeodomain Proteins
  • Trans-Activators
  • pancreatic and duodenal homeobox 1 protein
  • Aurka protein, mouse
  • Aurora Kinase A
  • Aurora Kinases
  • Protein Serine-Threonine Kinases