Thymic lymphomas are resistant to Nur77-mediated apoptosis.
We reported previously that thymic lymphomas from mice expressing transgenic TCR autoreactive against male (HY) antigen were resistant to anti-CD3 antibody-mediated induction of apoptosis although they were responding to TCR triggering. To test whether thymic lymphomas were specifically resistant to TCR-dependent Ca(++)-mediated induction of apoptosis, we have measured apoptosis of cells treated with Ca(++)-dependent (ionomycin, A23187) and Ca(++)-independent (etoposide, dexamethasone) inducers of apoptosis. Here we show that, unlike thymocytes, all thymic lymphomas were resistant to Ca(++)-dependent but not to Ca(++)-independent induction of apoptosis. These results excluded a general defect of apoptosis in lymphoma cells and suggested a specific inhibition of the calcium-mediated (TCR-dependent) pathway of apoptosis in lymphomas. Interestingly however, nuclear expression of a specific mediator of TCR-dependent apoptosis Nur77 was induced in ionomycin-resistant lymphomas indicating that, unlike normal thymocytes, thymic lymphomas are resistant to Nur77-mediated apoptosis.
Matuszyk
J
J
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Kobzdej
M
M
Ziolo
E
E
Kalas
W
W
Kisielow
P
P
Strzadala
L
L
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000473:pathology*; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D011948:Receptors, Antigen, T-Cell; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors