Effect of malignant transformation on lactate levels of human mammary epithelial cells

Eric O. Aboagye, Noriko Mori, Zaver M Bhujwalla

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalAdvances in Enzyme Regulation
Volume41
DOIs
Publication statusPublished - 2001

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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