The proto-oncogene c-fos mediates apoptosis in murine T-lymphocytes induced by ionizing radiation and dexamethasone.
Expression of the immediate early response gene c-fos is induced by several cellular and extracellular stress factors including ionizing radiation. We examined the role of c-fos in mediating stress-induced apoptosis of isogenic CD4+ and CD8+ mouse T-lymphocytes differing only in their c-fos status after treatment with ionizing radiation and the synthetic glucocorticoid dexamethasone. The amount of radiation-induced apoptosis was decreased (up to 37%) in the T-lymphocyte population derived from the knockout mice lacking endogenous c-fos compared to the wildtype T-lymphocyte population. The difference in apoptosis induction in T-lymphocytes from wildtype and c-fos knockout mice was even more prominent (up to 55%) after dexamethasone treatment. Comparative experiments were performed with T-lymphocytes from isogenic mouse littermates differing only in the status of the tumor-suppressor gene p53. Whereas p53 plays a primary role in radiation-induced apoptosis, our results suggest that c-fos enhances both p53-dependent radiation- and p53-independent steroid-induced apoptosis in T-lymphocytes.
Pruschy
M
M
Department of Radiation Oncology, University Hospital Zurich, Switzerland. pum@dmr.usz.ch and bost@dmr.usz.ch
Shi
Y Q
YQ
Crompton
N E
NE
Steinbach
J
J
Aguzzi
A
A
Glanzmann
C
C
Bodis
S
S
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016760:Proto-Oncogene Proteins c-fos / Q000172:deficiency* / Q000235:genetics; D011839:Radiation, Ionizing; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000187:drug effects / Q000528:radiation effects*
D005938:Glucocorticoids; D016760:Proto-Oncogene Proteins c-fos; D003907:Dexamethasone