A unique glucose-dependent apoptotic pathway inducedâbyâc-Myc Export

@article{citeulike:6081336, abstract = {The lactate dehydrogenase A () gene, whose product participates in normal anaerobic glycolysis and is frequently increased in human cancers, has been identified as a c-Myc-responsive gene. It was of interest, therefore, to compare the effect of glucose deprivation in c-Myc-transformed and nontransformed cells. We observed that glucose deprivation or treatment with the glucose antimetabolite 2-deoxyglucose caused nontransformed cells to arrest in the G/G phase of the cell cycle. In contrast, c-Myc-transformed fibroblasts, lymphoblastoid, or lung carcinoma cells underwent extensive apoptosis. Ectopic expression of alone in Rat1a fibroblasts was sufficient to induce apoptosis with glucose deprivation but not with serum withdrawal, suggesting that LDH-A mediates the unique apoptotic effect of c-Myc when glycolysis is blocked. The apoptosis caused by glucose deprivation was blocked by Bcl-2 expression but appeared to be independent of wild-type p53 activity. These studies provide insights on the coupling of glucose metabolism and the cell cycle in c-Myc-transformed cells and may in the future be exploited for cancer therapeutics.}, author = {Shim, Hyunsuk and Chun, Yoon S. and Lewis, Brian C. and Dang, Chi V.}, citeulike-article-id = {6081336}, citeulike-linkout-0 = {http://www.pnas.org/content/95/4/1511.abstract}, citeulike-linkout-1 = {http://www.pnas.org/content/95/4/1511.full.pdf}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/9465046}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=9465046}, day = {17}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {biology, cancer, flux, metabolic\_networks}, month = {February}, number = {4}, pages = {1511--1516}, posted-at = {2009-11-06 17:35:40}, priority = {2}, title = {A unique glucose-dependent apoptotic pathway induced\^{a}€‰by\^{a}€‰c-Myc}, url = {http://www.pnas.org/content/95/4/1511.abstract}, volume = {95}, year = {1998} }

TY - JOUR ID - citeulike:6081336 L3 - citeulike-article-id:6081336 N2 - The lactate dehydrogenase A () gene, whose product participates in normal anaerobic glycolysis and is frequently increased in human cancers, has been identified as a c-Myc-responsive gene. It was of interest, therefore, to compare the effect of glucose deprivation in c-Myc-transformed and nontransformed cells. We observed that glucose deprivation or treatment with the glucose antimetabolite 2-deoxyglucose caused nontransformed cells to arrest in the G/G phase of the cell cycle. In contrast, c-Myc-transformed fibroblasts, lymphoblastoid, or lung carcinoma cells underwent extensive apoptosis. Ectopic expression of alone in Rat1a fibroblasts was sufficient to induce apoptosis with glucose deprivation but not with serum withdrawal, suggesting that LDH-A mediates the unique apoptotic effect of c-Myc when glycolysis is blocked. The apoptosis caused by glucose deprivation was blocked by Bcl-2 expression but appeared to be independent of wild-type p53 activity. These studies provide insights on the coupling of glucose metabolism and the cell cycle in c-Myc-transformed cells and may in the future be exploited for cancer therapeutics. IS - 4 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 1516 TI - A unique glucose-dependent apoptotic pathway induced by c-Myc VL - 95 SP - 1511 KW - biology KW - cancer KW - flux KW - metabolic_networks AU - Shim, Hyunsuk AU - Chun, Yoon AU - Lewis, Brian AU - Dang, Chi PY - 1998/02/17/ UR - http://www.pnas.org/content/95/4/1511.abstract ER -