Vol. 62, Issue 6, 1400-1408, December 2002

c-Myc Exerts a Protective Function through Ornithine Decarboxylase against Cellular Insults

Jong Kuk Park, Young Min Chung, Seongman Kang, Jae-Uk Kim, Yun-Taik Kim, Hyung Jung Kim, Yeul Hong Kim, Jun Suk Kim, and Young Do Yoo

Korea University Cancer Institute (J.K.P., J.S.K., Y.D.Y.), Genomic Research Center for Lung and Breast/Ovarian Cancers (Y.H.K., Y.D.Y.), Brain Korea21 Biomedical Sciences (Y.M.C., J.S.K.), and Department of Internal Medicine (Y.H.K., J.S.K.), Korea University College of Medicine, Seoul, Korea; Department of Life Science, Sogang University, Seoul, Korea (J.K.P., Y.-T.K.); Graduate School of Biotechnology, Korea University, Seoul, Korea (S.K., J.-U.K.); and Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (H.J.K.)

c-Myc is known to control cell proliferation and apoptosis, and much effort has been focused on elucidating the mechanisms by which c-Myc works. In this study, we show that c-Myc expression is induced by many cellular insults, including cisplatin, doxorubicin, paclitaxel, 5-flourouracil, H₂O₂, and radiation, and the enhanced expression of c-Myc protects against cell death caused by these cellular insults through ornithine decarboxylase (ODC) induction. To investigate the cellular protective role of c-Myc, we constructed a stable transfectant of ODC, one of the many transcriptional targets of c-Myc in cells, and found that enhanced expression of ODC inhibited cell death induced by cellular insults such as cisplatin, H₂O_2, and radiation. We also found that cisplatin activated nuclear factor-B, and this subsequently induced c-Myc expression, resulting in the blocking of apoptosis through ODC induction. The results herein, therefore, strongly suggest another role for c-Myc in a stress-response function; that is, it promotes cell survival under stressful conditions.