Regulation of CD95 (Apo-1/Fas) Ligand and Receptor Expression in Human Embryonal Carcinoma Cells by Interferon γ and all-trans Retinoic Acid

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Abstract
Expression of CD95 (Apo-1/Fas) ligand and its two receptor isoforms, in response to all-trans retinoic acid and interferon gamma (IFNgamma), was analyzed atthe mRNA and protein levels in human Tera-2 embryonal 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 compared to the control conditions, whereas expression of both CD95 isoforms 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 bearing Jurkat T lymphocytes after six days of incubation with all-trans retinoic acid. When Tera-2 cells were treated with IFNgamma, expression of CD95 ligand and both CD95 receptor isoforms increased within 24 hours. Tera-2 cells were then more susceptible to CD95 mediated apoptosis but also killed more CD95 receptor bearing Jurkat T lymphocytes via CD95 ligation compared to the control conditions. The results are indicative of differential regulation of CD95-mediated apoptosis by all-trans retinoic acid and IFNgamma in Tera-2 embryonal carcinoma cells, with likely impact on antitumor immunity.