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Molecular phenotype of simian virus 40 large T antigen-induced primitive neuroectodermal tumors in four different
K M Fung1, D M Chikaraishi, C Suri
1Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia.
Background:
We compared the molecular phenotypes of central nervous system tumors arising in four different lines of transgenic mice (TGM) carrying the Simian virus 40 large T antigen driven by different promoters or enhancers. Two of the four lines developed primitive neuroectodermal tumors (PNETs) in the brain stem or pineal gland. A third TGM line developed retinoblastomas (a PNET-like tumor of the retina) as well as PNETs in the mesencephalon, while the fourth TGM developed retinoblastomas and adrenal pheochromocytomas.
Experimental Design:
The expression of developmentally regulated polypeptides specific for the neuronal or glial lineage was examined in these PNETs using immunohistochemistry and Western blotting.
Results:
Neoplastic cells in all of the PNETs exhibited neuronal, but no glial specific markers as evidenced by the invariable expression of synaptophysin, but no detectable glial fibrillary acidic protein or myelin basic protein. PNETs with a more differentiated neuronal phenotype expressed multiple neuronal polypeptides. The phenotypic properties of these PNETs closely resembled those found in human brain PNET biopsy samples and cell lines derived therefrom.
Conclusions:
We conclude that Simian virus 40 T antigen-induced PNETs in TGM exhibit the molecular phenotype of developing neurons or neuronal progenitor cells. Although many factors could influence the phenotype of these experimental PNETs (e.g., promoter, site of integration of the transgene) these PNETs appear to be suitable TGM models of human PNETs of the central nervous system.
Insights
Simian virus 40 T antigen-induced primitive neuroectodermal tumors (PNETs) in transgenic mice models exhibit molecular phenotypes of developing neurons. These models closely resemble human central nervous system PNETs, making them suitable for further study.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- Transgenic mice (TGM) carrying Simian virus 40 large T antigen were used to study central nervous system tumors.
- Four TGM lines developed various tumors, including primitive neuroectodermal tumors (PNETs) and retinoblastomas.
Purpose of the Study:
- To compare the molecular phenotypes of central nervous system tumors in different TGM lines.
- To investigate the suitability of these TGM-induced tumors as models for human PNETs.
Main Methods:
- Immunohistochemistry and Western blotting were employed to examine polypeptide expression.
- Specific markers for neuronal and glial lineages were analyzed in the developed PNETs.
Main Results:
- All PNETs consistently expressed neuronal markers (e.g., synaptophysin) but lacked glial markers (e.g., GFAP, MBP).
- More differentiated PNETs showed expression of multiple neuronal polypeptides.
- The molecular phenotype of these experimental PNETs mirrored human PNET biopsy samples and cell lines.
Conclusions:
- Simian virus 40 T antigen-induced PNETs in TGM display the molecular characteristics of developing neurons or neuronal progenitor cells.
- These TGM-induced PNETs serve as valuable models for studying human central nervous system PNETs.