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Transgenic mouse model for human gastric carcinoma
K Koike1, S H Hinrichs, K J Isselbacher
1Laboratory of Virology, Jerome H. Holland Laboratory, American Red Cross, Rockville, MD 20855.
Summary
Human adenovirus type 12 (Ad12) early region 1 gene products induce stomach tumors in male transgenic mice. This model aids research into carcinomas at squamous to columnar epithelial transition zones.
Area of Science:
- Oncology
- Virology
- Genetics
Background:
- Human adenovirus type 12 (Ad12) is a virus with oncogenic potential.
- Understanding Ad12 pathogenesis is crucial for cancer research.
- The Ad12 early region 1 (E1) genes are implicated in viral oncogenesis.
Purpose of the Study:
- To investigate the pathogenic effects of Ad12 early region 1 (E1) gene products.
- To develop a transgenic mouse model for studying Ad12-induced carcinogenesis.
- To explore the organ-specific activity of Ad12 E1 genes.
Main Methods:
- Generation of transgenic mice harboring the Ad12 E1 gene under the control of the mouse mammary tumor virus (MMTV) promoter.
- Monitoring founder mice for tumor development and survival rates.
- Histopathological analysis of tumors and gene expression analysis in various tissues.
Main Results:
- Male founder mice exhibited high mortality (11/11) between 3-4 months of age, while females showed lower mortality (2/12).
- Tumors, identified as adenocarcinomas or adenosquamous carcinomas, developed at the stomach's squamocolumnar junction.
- High Ad12 E1A and E1B gene expression was detected in stomach tumors, with varying levels in other organs.
Conclusions:
- Ad12 E1 gene products exhibit organ-specific carcinogenicity, primarily targeting the stomach.
- The developed transgenic mouse model effectively replicates human carcinomas at epithelial transition zones.
- This model serves as a valuable tool for studying the molecular mechanisms of Ad12-induced cancer development.