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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  ;  Young Do Yoo 
 MOLECULAR PHARMACOLOGY, Vol.62(6) : 1400-1408, 2002 
Journal Title
Issue Date
Antineoplastic Agents/pharmacology ; Cell Survival/physiology ; Cisplatin/pharmacology ; Enzyme Induction ; Gene Expression/drug effects ; Humans ; NF-kappa B/metabolism ; Ornithine Decarboxylase/biosynthesis* ; Ornithine Decarboxylase/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/physiology* ; Tumor Cells, Cultured
CDDP ; cis-diamminedichloroplatinum(II) ; HDF ; human dental fibroblast ; RPE ; retinal pigment epithelial ; NF- B ; nuclear factor- B ; ODC ; ornithine decarboxylase ; 5-FU ; 5-flourouracil ; ROS ; reactive oxygen species ; Gy ; gray ; GAPDH ; glyceraldehyde-3-phosphate dehydrogenase ; EMSA ; electrophoretic mobility shift assay ; PI, propidium iodide ; JNKDD ; dominant-negative c-Jun NH2-terminal kinase-1 mutant ; I BDD ; dominant-negative of I B mutant ; kbp ; kilobase pair
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, H2O2, and radiation. We also found that cisplatin activated nuclear factor-κB, 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.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hyung Jung(김형중) ORCID logo https://orcid.org/0000-0003-2498-0683
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