The exogenous control of transfected c- fos gene expression and angiogenesis in cells implanted into the rat brain

• Published in: Brain research 1995-12, Vol.702 (1), p.23-31
• Main Authors: Asakuno, Keizoh, Isono, Mitsuo, Wakabayashi, Yukihiro, Mori, Teruaki, Hori, Shigeaki, Kohno, Kimitoshi, Kuwano, Michihiko
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Biological and medical sciences; Brain Tissue Transplantation; c- fos gene; Cell Count - drug effects; Development. Senescence. Regeneration. Transplantation; Exogenous control; Fundamental and applied biological sciences. Psychology; Gene Expression - genetics; Gene therapy; Metallothionein promoter; Neovascularization; Nf-1 cell; NRK cell; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Inbred F344; RNA, Messenger - analysis; Transfection - genetics; Transplantation; Vertebrates: nervous system and sense organs; Zinc - pharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00880-8

Previously, we established a stable transfectant, Nf-1, from normal rat kidney (NRK) fibroblasts transfected with a human metallothionein II A (hMT-IIA) promoter/human genomic c- fos fusion gene to produce c-Fos protein. Since the hMT-IIA promoter can be activated by heavy metals, the level of human c- fos gene expression can be increased by addition of heavy metals to the culture medium of Nf-1 cells and the anchorage-independent growth of Nf-1 in soft agar is markedly enhanced in the presence of transforming growth factor-β (TGF-β) and epidermal growth factor (EGF). In this study, we found that the hMT-IIA promoter can be activated by zinc, resulting in the elevation of fused c- fos gene expression in Nf-1 cells. We transplanted NRK and Nf-1 cells into the striatum of the rat brain and investigated whether expression of the human c- fos gene could be modified in the brain by exogenous zinc. After 8 weeks, we found that the Nf-1 cells could survive in the rat brain without any immunosuppression and grafts of Nf-1 induced angiogenesis when zinc was administered. Such implants enhanced the expression of c- fos mRNA by zinc. These results indicated that the transplanted cells continued expressing the c- fos transgene when the rats were given drinking water containing zinc, resulting in the promotion of cell growth and of neovascularization. This study will present a useful animal model of gene therapy by control of transgene expression in the brain.