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Glucose Catabolism in Cancer Cells: Amplification of the Gene Encoding Type II Hexokinase¹

Departments of Biological Chemistry [A. R., S. P. M., P. L. P.] and Pathology [C. A. G., A. L. H.], The Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205-2185

Hexokinase type II is highly overexpressed in many cancer cells, where it plays a pivotal role in the high glycolytic phenotype. Here we demonstrate by Southern blot analysis and fluorescence in situ hybridization (FISH) that in the rapidly growing rat AS-30D hepatoma cell line, enhanced hexokinase activity is associated with at least a 5-fold amplification of the type II gene relative to normal hepatocytes. This amplification is located chromosomally, extends to the whole gene, and most likely occurs at the site of the resident gene. No rearrangement of the gene could be detected. Therefore, overexpression of hexokinase type II in AS-30D hepatoma cells may be based, at least in part, on a stable gene amplification. This is the first report describing the amplification of a hexokinase gene in a tumor cell line expressing the high glycolytic phenotype.

¹ Supported in part by NIH Grant CA 32742 (to P. L. P.) and NIH Grant 2P30-CA06972 (to C. A. G.). A. R. was an awardee of the Deutsche Forschungsgemeinschaft.

² To whom correspondence should be addressed, at Department of Biological Chemistry. The Johns Hopkins University, School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205-2185. Phone: (410) 955-3827; Fax: (410) 955-1944.

Received 3/12/96. Accepted 4/23/96.

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