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 therapy strategies for intestinal adenocarcinomas, carcinoembryonic antigen (CEA) promoter/SV40 T antigen gene constructs have been used to generate transgenic mice. One transgenic line (L5496), which contains a 424-bp CEA promoter/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 the mucosal layer. In 50-day-old mice, the tumor mass was mainly restricted to the mucosa with invasive growth into the submucosal tissue. The animals became moribund at 100-130 days of age due to blockage of the pylorus. At this time, the tumor had penetrated into the duodenum and had invaded all tissue layers within the stomach. In contrast to most other stomach tumor models, this one perfectly matches the development of the most common stomach cancers found in humans. Furthermore, after crossing these mice with mice that are transgenic for the human CEA gene, the double transgenic offspring revealed expression of CEA in the resulting tumors. Thus, as well as being a model for studying gastric carcinoma development and prevention, this system should provide a useful preclinical model for CEA-targeted gastric tumor therapy.
Thompson
J
J
Institute of Molecular Medicine and Cell Research, University of Freiburg, Freiburg, Germany.
Epting
T
T
Schwarzkopf
G
G
Singhofen
A
A
Eades-Perner
A M
AM
van Der Putten
H
H
Zimmermann
W
W
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics* / Q000502:physiology; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D015316:Genetic Therapy; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000209:etiology / Q000628:therapy*
D000952:Antigens, Polyomavirus Transforming; D002272:Carcinoembryonic Antigen