Angiogenic activity of the K-fgf/hst oncogene in neural transplants

O. Brustle, A. Aguzzi, D. Talarico, C. Basilico, P. Kleihues, O. D. Wiestler

Research output: Contribution to journalArticle

Abstract

Using retrovirus-mediated gene transfer into neural transplants, we have expressed the human K-fgf/hst oncogene in the central nervous system. Single-cell suspensions of fetal rat brains were removed at embryonic days 13 and 14, exposed to a retroviral vector encoding the K-fgf oncogene and stereotaxically implanted into the caudate putamen of syngenic adult Fisher rats. Recipient animals were sacrificed at intervals of 6-16 months without evidence of neurological impairment. Mock-infected grafts showed the characteristic histopathological appearance of organotypically differentiated neural transplants. In contrast, grafts exposed to K-fgf gene exhibited abundant capillary proliferation and capillary angiomas. By in situ hybridization analysis and immunohistochemistry, expression of K-fgf was detected in neural cells adjacent to vascular proliferations. Neurons and glia with abundant K-fgf transcripts were morphologically unaffected. In order to examine the transforming potential of the K-fgf gene in the nervous system, we combined retrovirus-mediated transfer of the K-fgf oncogene with a single transplacental exposure of the donor animals to the neurotropic carcinogen N-ethyl-N-nitrosourea (NEU). However, this combination of transforming agents did not result in tumor formation in the grafts. These results provide evidence for a powerful angiogenic effect of K-fgf on the developing brain in vivo.

Original languageEnglish
Pages (from-to)1177-1183
Number of pages7
JournalOncogene
Volume7
Issue number6
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

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  • Cite this

    Brustle, O., Aguzzi, A., Talarico, D., Basilico, C., Kleihues, P., & Wiestler, O. D. (1992). Angiogenic activity of the K-fgf/hst oncogene in neural transplants. Oncogene, 7(6), 1177-1183.