A transgenic mouse line that develops early-onset invasive gastric carcinoma provides a model for carcinoembryonic antigen-targeted tumor therapy

In an attempt to obtain suitable in vivo models for optimizing new tumor th erapy strategies for intestinal adenocarcinomas, carcinoembryonic antigen ( CEA) promoter/SV40 T antigen gene constructs have been used to generate tra nsgenic mice. One transgenic line (L5496), which contains a 424-bp CEA prom oter/SV40 T antigen transgene, exclusively developed multi-focal carcinomas in the pyloric region of the stomach in 100% of the offspring. Tumors were already observable in 37-day-old animals as dysplastic cell foci within th e mucosal layer. In 50-day-old mice, the tumor mass was mainly restricted t o the mucosa with invasive growth into the submucosal tissue. The animals b ecame moribund at 100-130 days of age due to blockage of the pylorus. At th is time, the tumor had penetrated into the duodenum and had invaded all tis sue layers within the stomach. In contrast to most other stomach tumor mode ls, this one perfectly matches the development of the most common stomach c ancers found in humans. Furthermore, after crossing these mice with mice th at are transgenic for the human CEA gene, the double transgenic offspring r evealed expression of CEA in the resulting tumors. Thus, as well as being a model for studying gastric carcinoma development and prevention, this syst em should provide a useful preclinical model for CEA-targeted gastric tumor therapy. Int. J. Cancer 86:863-869, 2000. (C) 2000 Wiley-Liss, Inc.