4.3 Article

Pdx-1-Driven Overexpression of Aurora A Kinase Induces Mild Ductal Dysplasia of Pancreatic Ducts Near Islets in Transgenic Mice

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PANCREAS
卷 37, 期 3, 页码 E39-E44

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MPA.0b013e318176b9ae

关键词

pancreatic adenocarcinoma; Aurora A kinase; transgenic mouse model

资金

  1. American Chemical Society
  2. Division of Medicinal Chemistry and Wyeth
  3. National Institutes of Health [CA 9503]

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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.

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