REGULATION OF CD95 (APO-1 FAS) LIGAND AND RECEPTOR EXPRESSION IN HUMAN EMBRYONAL CARCINOMA-CELLS BY INTERFERON-GAMMA AND ALL-TRANS-RETINOICACID/

Expression of CD95 [Apo-1/Fas) ligand and its two receptor isoforms, i n response to all-trans retinoic acid and interferon gamma (IFN gamma) , was analyzed at the mRNA and protein levels in human Tera-2 embryona l carcinoma cells. Exposure of Tera-2 cells to all-trans retinoic acid for up to 16 days led to a decrease of CD95 ligand expression when co mpared to the control conditions, whereas expression of both CD95 isof orms increased. These changes were functionally significant since Tera -2 cells treated with all-trans retinoic acid for six to 16 days were more susceptible to CD95-mediated apoptosis, On the other hand, Tera-2 cells lost their capacity to induce apoptosis in CD95 receptor bearin g Jurkat T lymphocytes after six days of incubation with all-trans ret inoic acid. When Tera-2 cells were treated with IFN gamma, expression of CD95 ligand and both CD95 receptor isoforms increased within 24 hou rs. Tera-2 cells were then more susceptible to CD95 mediated apoptosis but also killed more CD95 receptor bearing Jurkat T lymphocytes via C D95 ligation compared to the control conditions. The results are indic ative of differential regulation of CD95-mediated apoptosis by all-tra ns retinoic acid and IFN gamma in Tera-2 embryonal carcinoma cells, wi th likely impact on antitumor immunity.