c-Myc Exerts a Protective Function through Ornithine Decarboxylase against Cellular Insults
- Jong Kuk Park1,5,
- Young Min Chung3,
- Seongman Kang6,
- Jae-Uk Kim6,
- Yun-Taik Kim5,
- Hyung Jung Kim7,
- Yeul Hong Kim2,4,
- Jun Suk Kim1,3,4 and
- Young Do Yoo1,2
- 1Korea University Cancer Institute (J.K.P., J.S.K., Y.D.Y.), 2Genomic Research Center for Lung and Breast/Ovarian Cancers (Y.H.K., Y.D.Y.),3Brain Korea21 Biomedical Sciences (Y.M.C., J.S.K.), and 4Department of Internal Medicine (Y.H.K., J.S.K.), Korea University College of Medicine, Seoul, Korea; 5Department of Life Science, Sogang University, Seoul, Korea (J.K.P., Y.-T.K.); 6Graduate School of Biotechnology, Korea University, Seoul, Korea (S.K., J.-U.K.); and 7Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (H.J.K.)
- Dr. Young Do Yoo, Genomic Research Center for Lung and Breast/Ovarian Cancers, Korea University Cancer Institute, Korea University College of Medicine, Anam Hospital, 126–1, 5ka, Anam-dong, Sungbuk-ku, Seoul 136-705, Korea. E-mail:ydy{at}kumc.or.kr
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, 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.
Footnotes
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This work was supported by the National Nuclear Research and Development Program from the Ministry of Science and Technology of Korea and the Brain Korea 21 Project in 2002. Work at Yonsei University College of Medicine was supported by grant 2000–2-20800–001-3 from the Basic Research Program of the Korea Science and Engineering Foundation.
- Abbreviations:
- CDDP
- cis-diamminedichloroplatinum(II)
- HDF
- human dental fibroblast
- RPE
- retinal pigment epithelial
- NF-κB
- nuclear factor-κB
- 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
- IκBDD
- dominant-negative of IκBα mutant
- kbp
- kilobase pair
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- Received April 2, 2002.
- Accepted September 3, 2002.
- The American Society for Pharmacology and Experimental Therapeutics
