Bailey J M, Wu J D
J Lipid Res. 1977 Jul;18(4):512-6.
The loss in feedback control of cholesterol biosynthesis in tumor cells was examined in tissue culture. Human fibroblasts from normal subjects, SV40 tumor virus-transformed 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 (125)I-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.
在组织培养中研究了肿瘤细胞胆固醇生物合成反馈控制的丧失情况。以来自正常受试者的人成纤维细胞、SV40肿瘤病毒转化的细胞系以及纯合子家族性高胆固醇血症细胞作为对照，在组织培养中进行培养。开展实验以研究胆固醇生物合成的调节酶HMG CoA还原酶，以及介导正常细胞中反馈控制的低密度脂蛋白（LDL）膜结合受体。病毒转化的肿瘤细胞单层对（125）I标记的LDL的特异性结合为152±21 ng/mg细胞蛋白，这与正常成纤维细胞（135±20 ng/mg）基本相同。在相同测试条件下，用作对照的家族性高胆固醇血症细胞对LDL的结合仅为8±3 ng/mg。肿瘤细胞中HMG CoA还原酶的基础水平为45.2±6.5单位/mg细胞蛋白，约为正常细胞的两倍。然而，与体内肿瘤中观察到的该酶缺乏反馈控制相反，在体外的正常细胞和转化细胞中，当添加血清脂质时，该酶的活性下降约四倍。这些发现表明，体外生长的肿瘤细胞含有正常数量的低密度脂蛋白膜结合受体，并且尽管基础水平高于正常，但HMG CoA还原酶仍保留有效的反馈调节。
