Regulation of CD95 (Apo-1/Fas) ligand and receptor expression in human embryonal carcinoma cells by interferon gamma and all-trans retinoic acid.
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.
Müschen
M
M
Klinik für Gastroenterologie, Hepatologie und Infektiologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Warskulat
U
U
Schmidt
B
B
Schulz
W A
WA
Häussinger
D
D
D017209:Apoptosis; D001483:Base Sequence; D018236:Carcinoma, Embryonal / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D053222:Fas Ligand Protein; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000235:genetics*
D017931:DNA Primers; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; D014212:Tretinoin; D007371:Interferon-gamma