A Unique Glucose-Dependent Apoptotic Pathway Induced by c-Myc

The lactate dehydrogenase A (LDH-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 nontr...

Full description

Saved in:
Bibliographic Details
Published inProceedings of the National Academy of Sciences - PNAS Vol. 95; no. 4; pp. 1511 - 1516
Main Authors Shim, Hyunsuk, Chun, Yoon S., Lewis, Brian C., Dang, Chi V.
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences of the United States of America 17.02.1998
National Acad Sciences
National Academy of Sciences
The National Academy of Sciences
Subjects
Animals
Apoptosis
Biological Sciences
Cancer
Cell cycle
Cell death
Cell growth
Cell lines
Cells, Cultured
Cellular biology
Cultured cells
Deoxyglucose - pharmacology
Fibroblasts
Gene Expression Regulation, Enzymologic
Genes
Genes, myc
Glucose
Glucose - metabolism
Glycolysis
Humans
L-Lactate Dehydrogenase - physiology
Lymphocytes
Mice
Proto-Oncogene Proteins c-bcl-2 - physiology
Proto-Oncogene Proteins c-myc - physiology
Rats
Transfection
Transformed cell line
Tumor Suppressor Protein p53 - physiology
Online AccessGet full text

Cover

More Information
Summary:The lactate dehydrogenase A (LDH-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 G0/G1phase of the cell cycle. In contrast, c-Myc-transformed fibroblasts, lymphoblastoid, or lung carcinoma cells underwent extensive apoptosis. Ectopic expression of LDH-A 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.
Bibliography:ObjectType-Article-2
SourceType-Scholarly Journals-1
ObjectType-Feature-1
content type line 23
Edited by Stanley J. Korsmeyer, Washington University School of Medicine, St. Louis, MO, and approved December 12, 1997
To whom reprint requests should be addressed at: Ross Research Building, Room 1025, Johns Hopkins Medical School, 720 Rutland Avenue, Baltimore, MD 21205. e-mail: cvdang@welchlink.welch.jhu.edu.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.95.4.1511