HIGH-LEVELS OF C-REL EXPRESSION ARE ASSOCIATED WITH PROGRAMMED CELL-DEATH IN THE DEVELOPING AVIAN EMBRYO AND IN BONE-MARROW CELLS IN-VITRO

To determine the physiological processes in which the transcription fa ctor c-Rel may act, we have examined its pattern of expression in the avian embryo by in situ hybridization. These studies showed that c-rel is expressed ubiquitously at low levels and at high levels in isolate d cells undergoing programmed cell death by apoptosis or autophagocyto sis. To further establish a functional link between expression of c-re l and cell death, we examined the biological consequences of c-rel ove rexpression in vitro. In primary avian fibroblasts, overexpression of c-rel leads to transformation and dramatic life span extension. In con trast, bone marrow cells expressing high levels of c-rel undergo a pro cess of programmed cell death displaying features of both apoptosis an d autophagocylic cell death. Thus, these experiments suggest a critica l role for c-rel not only in the control of cell proliferation, but al so in the induction of cell death.