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

作者: John Thompson , Thomas Epting , Georg Schwarzkopf , Axel Singhofen , Anne-Marie Eades-Perner

DOI: 10.1002/(SICI)1097-0215(20000615)86:6<863::AID-IJC16>3.0.CO;2-4

关键词: PathologyPylorusStomachPyloric regionDuodenumBiologyTransgeneGenetically modified mouseCarcinoembryonic antigenGenetic enhancement

摘要: In an attempt to obtain suitable in vivo models for optimizing new tumor therapy strategies intestinal adenocarcinomas, carcinoembryonic antigen (CEA) promoter/SV40 T gene constructs have been used generate transgenic mice. One line (L5496), which contains a 424-bp CEA transgene, exclusively developed multi-focal carcinomas the pyloric region of stomach 100% offspring. Tumors were already observable 37-day-old animals as dysplastic cell foci within mucosal layer. 50-day-old mice, mass was mainly restricted mucosa with invasive growth into submucosal tissue. The became moribund at 100-130 days age due blockage pylorus. At this time, had penetrated duodenum and invaded all tissue layers stomach. contrast most other models, one perfectly matches development common cancers found humans. Furthermore, after crossing these mice that are human gene, double offspring revealed expression resulting tumors. Thus, well being model studying gastric carcinoma prevention, system should provide useful preclinical CEA-targeted therapy.

参考文章(32)
Enrique Gómez-La-Hoz, Enrique Gómez-La-Hoz, Roman Halter, Miguel Beato, Guntram Suske, Andrea Sandmöller, Hermann Josef Gröne, Dieter Paul, The uteroglobin promoter targets expression of the SV40 T antigen to a variety of secretory epithelial cells in transgenic mice Oncogene. ,vol. 9, pp. 2805- 2815 ,(1994)
Fumihiko Kanai, Torao Tanaka, Makoto Ohashi, Keng-Hsin Lan, Hirofumi Hamada, Takehito Okudaira, Yasushi Shiratori, Yoko Yoshida, Masao Omata, In vivo selective gene expression and therapy mediated by adenoviral vectors for human carcinoembryonic antigen-producing gastric carcinoma. Cancer Research. ,vol. 57, pp. 4279- 4284 ,(1997)
Wendy Hauck, Clifford P. Stanners, Transcriptional regulation of the carcinoembryonic antigen gene. Identification of regulatory elements and multiple nuclear factors. Journal of Biological Chemistry. ,vol. 270, pp. 3602- 3610 ,(1995) , 10.1074/JBC.270.8.3602
F M Botteri, H van der Putten, D F Wong, C A Sauvage, R M Evans, Unexpected thymic hyperplasia in transgenic mice harboring a neuronal promoter fused with simian virus 40 large T antigen. Molecular and Cellular Biology. ,vol. 7, pp. 3178- 3184 ,(1987) , 10.1128/MCB.7.9.3178
S Y Ng, P Gunning, R Eddy, P Ponte, J Leavitt, T Shows, L Kedes, Evolution of the functional human beta-actin gene and its multi-pseudogene family: conservation of noncoding regions and chromosomal dispersion of pseudogenes. Molecular and Cellular Biology. ,vol. 5, pp. 2720- 2732 ,(1985) , 10.1128/MCB.5.10.2720
J A Whitsett, K A Wikenheiser, M T Stahlman, R I Linnoila, J C Clark, Simian Virus 40 Large T Antigen Directed by Transcriptional Elements of the Human Surfactant Protein C Gene Produces Pulmonary Adenocarcinomas in Transgenic Mice Cancer Research. ,vol. 52, pp. 5342- 5352 ,(1992)
Hiroyasu Konishi, Takahiro Ochiya, Kerry A. Chester, Richard H. J. Beǵent, Tetsuichiro Muto, Takashi Sugimura, Masaaki Terada, Targeting Strategy for Gene Delivery to Carcinoembryonic Antigen-Producing Cancer Cells by Retrovirus Displaying a Single-Chain Variable Fragment Antibody Human Gene Therapy. ,vol. 9, pp. 235- 248 ,(1998) , 10.1089/HUM.1998.9.2-235
E. M. Garabedian, P. A. Humphrey, J. I. Gordon, A Transgenic Mouse Model of Metastatic Prostate Cancer Originating from Neuroendocrine Cells Proceedings of the National Academy of Sciences of the United States of America. ,vol. 95, pp. 15382- 15387 ,(1998) , 10.1073/PNAS.95.26.15382
M C Zennaro, D Le Menuet, S Viengchareun, F Walker, D Ricquier, M Lombès, Hibernoma development in transgenic mice identifies brown adipose tissue as a novel target of aldosterone action. Journal of Clinical Investigation. ,vol. 101, pp. 1254- 1260 ,(1998) , 10.1172/JCI1915