ANTI-IGM-INDUCED GROWTH-INHIBITION AND APOPTOSIS ARE INDEPENDENT OF ORNITHINE DECARBOXYLASE IN RAMOS CELLS

Ornithine decarboxylase (ODC) is a key enzyme involved in polyamine pr oduction and is thought to regulate growth and apoptosis in multiple c ell systems. A potential link between ODC and growth may involve the a ction of an oncogene c-myc which is thought to transcriptionally regul ate ODC. We have examined the involvement of ODC in anti-IgM-induced g rowth inhibition and apoptosis in Burkitt's lymphoma cells. Inhibitors of ODC such as difluoromethylornithine (DFMO) completely blocked ODC activity, resulting in growth inhibition but not apoptosis. Addition o f putrescine, the product of ODC enzymatic action, to Ramos cells had only a minor effect on growth, did not cause apoptosis, did not augmen t or block anti-IgM-mediated growth inhibition and apoptosis, but did reverse DFMO-mediated growth inhibition. Anti-IgM treatment of Ramos c ells, which markedly decreased c-myc mRNA and protein, caused a parado xical increase in ODC mRNA level as well as ODC enzymatic activity and increased cellular levels of putrescine. DFMO and putrescine did not alter c-myc mRNA levels directly, nor did they have any affects on ant i-IgM-mediated down-regulation of c-myc mRNA. TNF-alpha, which inhibit ed anti-IgM-mediated apoptosis, did not inhibit either anti-IgM or DFM O-mediated inhibition of growth. These agents mere without effect on O DC activity itself or on the anti-IgM-mediated increase in ODC activit y. From these studies we conclude that ODC inhibition affects growth b ut is unrelated to the induction of apoptosis. Both anti-IgM-mediated inhibition of growth and induction of apoptosis are independent of ODC . Thus two distinct pathways for growth regulation are present: one in which ODC and polyamines are important and the other cell surface rec eptor-mediated (sIg) which is independent of ODC and polyamines. (C) 1 997 Academic Press.