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Journal of Lipid Research, Vol. 18, 512-516, July 1977
Copyright © 1977 by Lipid Research, Inc.

Lipid metabolism in cultured cells XVI. Lipoprotein binding and HMG CoA reductase levels in normal and tumor virus-transformed human fibroblasts

J. Martyn Bailey and Jiunn-Der Wu

Department of Biochemistry, The George Washington University School of Medicine, Washington, DC 20037

The loss in feedback control of cholesterol biosynthesis in tumor cells was examined in tissue culture. Human fibroblasts from normal subjects, SV40 tumor virustransformed cell lines, and homozygous familial hypercholesterolemic cells as reference, were grown in tissue culture. Experiments were conducted to relate the regulatory enzyme for cholesterol biosynthesis, HMG CoA reductase, and the membrane-located binding receptors for low density lipoproteins (LDL) that mediate feedback control in normal cells. Monolayers of virus-transformed tumor cells exhibited specific ¹²⁵I-labeled LDL binding of 152 ± 21 ng/mg cell protein, which was essentially the same as that of normal fibroblasts (135 ± 20 ng/mg). Binding of LDL by familial hypercholesterolemic cells used as controls was only 8 ± 3 ng/mg under the same test conditions. Basal levels of HMG CoA reductase in tumor cells of 45.2 ± 6.5 units/mg cell protein were about twice those of normal cells. However, in contrast to the lack of feedback control of this enzyme observed with tumors in vivo, in both the normal and the transformed cells in vitro, activity of the enzyme decreased about fourfold when serum lipids were added. These findings demonstrate that tumor cells growing in vitro contain a normal complement of the membrane-located binding receptors for low density lipoproteins and, although the basal levels are higher than normal, an effective feedback regulation of the enzyme HMG CoA reductase is retained.

Supplementary key words lipoproteins • tissue culture • tumor cells • HMG CoA reductase • feedback control • cholesterol synthesis

Submitted on October 18, 1976
Accepted on March 16, 1977

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