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Cell Growth & Differentiation Vol. 10, 565-573, August 1999
© 1999 American Association for Cancer Research

Ecotropic Viral Integration Site-1 Is Activated during, and Is Sufficient for, Neuroectodermal P19 Cell Differentiation1

Hiroshi Kazama, Takao Kodera, Seiichi Shimizu, Hideaki Mizoguchi and Kazuhiro Morishita2

Biology Division, National Cancer Center Research Institute, Tokyo 104-0045 [H. K., T. K., S. S., K. M.]; and Department of Hematology, Tokyo Women’s Medical University, Tokyo 162-0054 [H. K., H. M.], Japan

Expression of the ecotropic viral integration site-1 (Evi1) proto-oncogene during murine embryonal development is observed by in situ hybridization in primary head folds and neural crest-derived cells associated with the peripheral nervous system and embryonic mesoderm. To elucidate whether expression of Evi1 is involved in early neuroectodermal or mesodermal differentiation, we used murine embryonal carcinoma P19 cells as a model for the study of early embryonic differentiation. After retinoic acid (RA) treatment with aggregation, expression of Evi1 was detected during neural differentiation in P19 cells. However, Evi1 was not expressed in P19 cells during mesodermal differentiation after DMSO treatment with aggregation. Enforced expression of Evi1 in P19 cells induced neuron-specific microtubule-associated protein-2 microtubule-associated protein-2 and TrkA expression in the absence of RA under monolayer culture. After incubation with RA with aggregation, the Evi1 clones expressed microtubule-associated protein-2 continuously but did not express glial fibrillary acidic protein as an astrocyte marker protein until 12 days of culture. Thus, the overexpression of Evi1 leads to neural differentiation of P19 cells and blocks further differentiation into astrocytes by RA treatment, suggesting that Evi1 might be an important transcription factor for regulation of early neuroectodermal differentiation.




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 1999 by the American Association of Cancer Research.