TY - JOUR
T1 - Effect of malignant transformation on lactate levels of human mammary epithelial cells
AU - Aboagye, Eric O.
AU - Mori, Noriko
AU - Bhujwalla, Zaver M.
N1 - Funding Information:
This work was supported by USAMRMC Grant DAMD-17-96-1-6131. We are grateful to Dr. Martha Stampfer of Berkeley National Laboratory (Berkeley, CA) for kindly donating the HMEC's used in this study and for useful suggestions. We thank Dr. V.P. Chacko, Dr. H. Shim and Mr. Gary Cromwell for expert assistance during the experiments.
PY - 2001
Y1 - 2001
N2 - Lactate is produced during glycolysis from pyruvate by the action of lactate dehydrogenase (LDH; EC 1. 1.1.27). To understand the relationship between the multi-step process of carcinogenesis of mammary epithelial cells and regulation of lactate levels, we studied a series of mammary epithelial cells representing various stages of transformation including normal (senescent/mortal) cells, spontaneously/benzo(a)pyrene immortalized cells, erbB2 oncogene transformed immortalized cells, and tumor-derived cells. 1. In our model system, intracellular lactate levels were low in normal cells and remained low after immortalization. Further transformation of benzo(a)pyrene immortalized cells by the erbB2 oncogene did not increase lactate levels. In contrast, all tumor-derived cells showed significantly higher lactate levels compared to the normal, immortalized and oncogene transformed cells (p ≤ 0.05). These studies suggest that the phenotype of increased lactate levels occurs late in carcinogenesis and supports our central hypothesis that multiple genes involved in malignant progression regulate the high lactate phenotype. 2. There was no correlation between intracellular lactate levels and cell doubling time. This suggests that increased glycolysis is not a prerequisite for growth. 3. Although the most metastatic of the cell lines had the highest lactate level and LDH activity, there was no overall association between lactate levels and LDH activity. This suggests that LDH is in great excess and may not be rate limiting. These studies are important in the use of lactate as a marker of malignancy or of response to therapy in patients.
AB - Lactate is produced during glycolysis from pyruvate by the action of lactate dehydrogenase (LDH; EC 1. 1.1.27). To understand the relationship between the multi-step process of carcinogenesis of mammary epithelial cells and regulation of lactate levels, we studied a series of mammary epithelial cells representing various stages of transformation including normal (senescent/mortal) cells, spontaneously/benzo(a)pyrene immortalized cells, erbB2 oncogene transformed immortalized cells, and tumor-derived cells. 1. In our model system, intracellular lactate levels were low in normal cells and remained low after immortalization. Further transformation of benzo(a)pyrene immortalized cells by the erbB2 oncogene did not increase lactate levels. In contrast, all tumor-derived cells showed significantly higher lactate levels compared to the normal, immortalized and oncogene transformed cells (p ≤ 0.05). These studies suggest that the phenotype of increased lactate levels occurs late in carcinogenesis and supports our central hypothesis that multiple genes involved in malignant progression regulate the high lactate phenotype. 2. There was no correlation between intracellular lactate levels and cell doubling time. This suggests that increased glycolysis is not a prerequisite for growth. 3. Although the most metastatic of the cell lines had the highest lactate level and LDH activity, there was no overall association between lactate levels and LDH activity. This suggests that LDH is in great excess and may not be rate limiting. These studies are important in the use of lactate as a marker of malignancy or of response to therapy in patients.
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U2 - 10.1016/S0065-2571(00)00019-4
DO - 10.1016/S0065-2571(00)00019-4
M3 - Article
C2 - 11384749
AN - SCOPUS:0034994670
SN - 0065-2571
VL - 41
SP - 251
EP - 260
JO - Advances in Enzyme Regulation
JF - Advances in Enzyme Regulation
IS - 1
ER -