Targeted Expression of Human MYCN Selectively Causes Pancreatic Neuroendocrine Tumors in Transgenic Zebrafish
- Yang, H.W., Kutok, J.L., Lee, N.H., Piao, H.Y., Fletcher, C.D., Kanki, J.P., and Look, A.T.
- Cancer research 64(20): 7256-7262 (Journal)
- Registered Authors
- Kanki, John, Look, A. Thomas
- MeSH Terms
- Animals, Genetically Modified
- Carcinoma, Islet Cell/genetics
- Carcinoma, Islet Cell/metabolism
- Islets of Langerhans/pathology
- Neuroectodermal Tumors/genetics*
- Neuroectodermal Tumors/metabolism
- Nuclear Proteins/biosynthesis
- Nuclear Proteins/genetics*
- Oncogene Proteins/biosynthesis
- Oncogene Proteins/genetics*
- Pancreatic Neoplasms/genetics*
- Pancreatic Neoplasms/metabolism
- Promoter Regions, Genetic
- RNA, Messenger/biosynthesis
- RNA, Messenger/genetics
- 15492244 Full text @ Cancer Res.
Yang, H.W., Kutok, J.L., Lee, N.H., Piao, H.Y., Fletcher, C.D., Kanki, J.P., and Look, A.T. (2004) Targeted Expression of Human MYCN Selectively Causes Pancreatic Neuroendocrine Tumors in Transgenic Zebrafish. Cancer research. 64(20):7256-7262.
The zebrafish model organism has been used extensively for studies of genetic pathways in development, indicating its potential applicability to cancer. Here we show that targeted expression of MYCN in cells of the pancreatic islet induces neuroendocrine carcinoma. Four transgenic fish developed abdominal tumors between 4 and 6 months of age, and histologic analysis revealed lobulated arrangements of neoplastic cells with expression of the MYCN transgene. The tumors also expressed insulin mRNA, and pancreatic exocrine cells and ducts were identified within the neoplasms, indicating a pancreatic origin for the tumor. Transmission electron microscopy revealed cytoplasmic, endocrine-dense core granules, analogous to those found in human neuroendocrine tumors. Our studies establish a zebrafish transgenic model of pancreatic neuroendocrine carcinoma, setting the stage to evaluate molecular pathways downstream of MYCN in this vertebrate forward genetic model system.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes