title: c-Myc exerts a protective function through ornithine decarboxylase against cellular insults.
abstract: 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, H(2)O(2), 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, H(2)O(2,) and radiation. We also found that cisplatin activated nuclear factor-kappaB, 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.
authors.affiliation: Korea University Cancer Institute, Korea University College of Medicine, Seoul, Korea.
authors.forename: Jong Kuk
authors.initials: JK
authors.lastname: Park
authors.forename: Young Min
authors.initials: YM
authors.lastname: Chung
authors.forename: Seongman
authors.initials: S
authors.lastname: Kang
authors.forename: Jae-Uk
authors.initials: JU
authors.lastname: Kim
authors.forename: Yun-Taik
authors.initials: YT
authors.lastname: Kim
authors.forename: Hyung Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Yeul Hong
authors.initials: YH
authors.lastname: Kim
authors.forename: Jun Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Young Do
authors.initials: YD
authors.lastname: Yoo
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D002945:Cisplatin / Q000494:pharmacology; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000096:biosynthesis* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; D016271:Proto-Oncogene Proteins c-myc; D009955:Ornithine Decarboxylase; D002945:Cisplatin