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Volume 272, Number 8, Issue of February 21, 1997 pp. 4941-4952
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

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Effect of Extracellular AMP on Cell Proliferation and Metabolism of Breast Cancer Cell Lines with High and Low Glycolytic Rates

(Received for publication, June 26, 1996, and in revised form, October 15, 1996)

Sybille Mazurek , Andrea Michel ^¶ and Erich Eigenbrodt

From the  Institut for Biochemistry and Endocrinology, Veterinary Faculty, Justus-Liebig-University Giessen, Frankfurter Straße 100, 35392 Giessen and ^¶ ScheBo Tech GmbH, Bahnhofstraße 6, 35435 Wettenberg, Federal Republic of Germany

In differentiated tissues, such as muscle and brain, increased adenosine monophosphate (AMP) levels stimulate glycolytic flux rates. In the breast cancer cell line MCF-7, which characteristically has a constantly high glycolytic flux rate, AMP induces a strong inhibition of glycolysis. The human breast cancer cell line MDA-MB-453, on the other hand, is characterized by a more differentiated metabolic phenotype. MDA-MB-453 cells have a lower glycolytic flux rate and higher pyruvate consumption than MCF-7 cells. In addition, they have an active glycerol 3-phosphate shuttle. AMP inhibits cell proliferation as well as NAD and NADH synthesis in both MCF-7 and MDA-MB-453 cells. However, in MDA-MB-453 cells glycolysis is slightly activated by AMP. This disparate response of glycolytic flux rate to AMP treatment is presumably caused by the fact that the reduced NAD and NADH levels in AMP-treated MDA-MB-453 cells reduce lactate dehydrogenase but not cytosolic glycerol-3-phosphate dehydrogenase reaction. Due to the different enzymatic complement in MCF-7 cells, proliferation is inhibited under glucose starvation, whereas MDA-MB-453 cells grow under these conditions. The inhibition of cell proliferation correlates with a reduction in glycolytic carbon flow to synthetic processes and a decrease in phosphotyrosine content of several proteins in both cell lines.

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