caa a22 4500 469073659 CHVBK 20180323132928.0 cr unu---uuuuu 170328e19921101xx s 000 0 eng 10.1007/BF01789017 doi (NATIONALLICENCE)springer-10.1007/BF01789017 In vivo tumorigenicity and in vitro sensitivity to tumor-necrosis-factorα mediated killing of c-Ha- ras -transformed cells [Elektronische Daten] [Bosmat Gonen, Orlie Kahana, Isaac Witz] Summary: Cellular subclones of high and low tumorigenicity obtained from a mouse c-Ha-ras-transformed clone, were examined for their sensitivity to tumornecrosis-factor (TNF)-mediated cytotoxicity. Cells of the highly tumorigenic subclones showed a significantly enhanced resistance to the cytotoxic effect of TNF plus cyclohexamide (CHI) as compared to cells of the lowtumorigenic subclones. The enhanced resistance to TNF+CHI was not due to a lower expression of TNF receptors on the cells. The c-Ha-ras-transfected cells were transformed and maintained in culture only (C cells). In vivo passage of cells of the initially low-tumorigenic c-Ha-ras subclones through the mouse significantly enhanced the tumorigenic potential of these CTC cells (culture/tumor/culture). In correlation with their enhanced tumorigenicity, the CTC cells were highly resistant to TNF-mediated cytotoxicity as compared to C cells of the same subclone. Furthermore, the involvement of TNF in determining the tumorigenic phenotype of the c-Ha-ras-transformed cells was demonstrated in a more direct manner. Cells of a c-Ha-ras-transformed low-tumorigenic, highly TNF-sensitive subclone were selected by repeated cycles of in vitro exposure to TNFα. As a result, a stable, highly TNF-resistant population of cells emerged. These TNF-resistant cells caused more tumors in mice as compared to their original TNF-sensitive cells. These results show that the resistance to the cytotoxic effect of TNF plus cyclohexamide may be involved, at least partially, in the tumorigenic potential of c-Ha-ras-transformed cells and suggest a possible role for TNF in the enhancement of the tumorigenic potential of these cells in mice. Springer-Verlag, 1992 Tumor necrosis factor α nationallicence c-Ha- ras -transformed cells nationallicence Tumor immunogenicity nationallicence Cytotoxicity nationallicence Gonen Bosmat Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69 978, Tel Aviv, Israel aut Kahana Orlie Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69 978, Tel Aviv, Israel aut Witz Isaac Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69 978, Tel Aviv, Israel aut Cancer Immunology, Immunotherapy Springer-Verlag 35/6(1992-11-01), 388-394 0340-7004 35:6<388 1992 35 262 https://doi.org/10.1007/BF01789017 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01789017 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gonen Bosmat Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69 978, Tel Aviv, Israel aut NATIONALLICENCE 700 1- Kahana Orlie Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69 978, Tel Aviv, Israel aut NATIONALLICENCE 700 1- Witz Isaac Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, 69 978, Tel Aviv, Israel aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/6(1992-11-01), 388-394 0340-7004 35:6<388 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer