Characterization of pancreatic lesions from MT-<it>tgf</it>&#945;, Ela-<it>myc </it>and MT-<it>tgf</it>&#945;/Ela-<it>myc </it>single and double transgenic mice

• Main Authors: Liao Dezhong, Wang Yong, Wu Jiusheng, Adsay Nazmi, Grignon David, Khanani Fayyaz, Sarkar Fazlul
• Format: Article
• Language: English
• Published: Wolters Kluwer Medknow Publications 2006-01-01
• Series: Journal of Carcinogenesis
• Online Access: http://www.carcinogenesis.com/content/5/1/19

<p>Abstract</p> <p>In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-<it>tgf</it>&#945; mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-<it>tgf</it>&#945;-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-<it>tgf</it>&#945;-ES lines, TGF&#945; transgene was expressed mainly in proliferating ductal cells. Ela-<it>myc </it>transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2&#8211;7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren <it>et al </it><abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-<it>myc </it>and MT-<it>tgf</it>&#945;-ES/Ela-<it>myc </it>double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-<it>myc </it>tumors. Sequencing of the coding region of <it>p16ink4</it>, k-<it>ras </it>and <it>Rb </it>cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-<it>myc </it>and MT-<it>tgf</it>&#945;/Ela-<it>myc </it>mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.</p>