C-FOS IS NOT ESSENTIAL FOR APOPTOSIS

The transcription factor AP-1, made up of dimers of Fos and Jun proto- oncogene products, is involved in distinct cellular processes, includi ng cell proliferation, differentiation and apoptosis. In this study, w e have used mice in which both copies of the c-fos gene were disrupted by targeted mutagenesis in order to analyze how the apoptotic respons e was affected in these mice. We prepared primary cultures from the ly mphoid organs, spleen and thymus, obtained from both wild-type and c-f os -/- mice and analyzed the induction of apoptosis in these cultures in the absence and presence of etoposide, an inducer of apoptosis in d istinct cell types. Primary cultures from both organs, spleen and thym us, isolated from wild-type mice underwent apoptosis after 3 and 6 h o f culture, respectively. Addition of etoposide enhanced the apoptotic response and c-fos mRNA levels in both spleen and thymic cells. Nevert heless, we Found that induction of apoptosis in primary cultures of ce lls obtained from spleen and thymus of c-Fos-deficient mice was practi cally identical to that observed in wild-type mice. These results demo nstrate that c-Fos is not essential for apoptosis and that cells lacki ng c-Fos may undergo normal apoptosis. (C) 1996 Academic Press, Inc.