Osborne C K, Bolan G, Monaco M E, Lippman M E
Proc Natl Acad Sci U S A. 1976 Dec;73(12):4536-40. doi: 10.1073/pnas.73.12.4536.
The mechanisms of steroid and peptide hormone action in human breast cancer are poorly understood. We have previously characterized a cell line of human breast cancer in long-term tissue culture that possesses various steroid hormone receptors and responses, providing a model for the study of steroid hormone action. The present studies describe a human breast cancer in vitro that responds to physiologie concentrations of insulin with an increased rate of macromolecular synthesis and growth. Thymidine and uridine incorporation in cells in serum-free medium are stimulated by 10(-11) M insulin and are maximal with 10(-8) M. Leucine incorporation is stimulated by 5 X 10(-11) M insulin and is maximal with 10(-9) M. Significant stimulation of uridine and leucine incorporation is evident by 3 hr and maximal by 10 hr. A 10-hr lag period exists for insulin stimulation of thymidine incorporation, which is maximal form 14 to 24 hr. The effect of 10(-8) M insulin on macromolecular synthesis is accompanied by a 69% increase above controls in the number of cells after 24 hr. The effect on macromolecular synthesis is observed in glucose-free medium. Insulin's effect on protein synthesis is not blocked by inhibition of RNA synthesis with actinomycin D. Glucocorticoids partially inhibit the action of insulin in these cells. This system provides a model for studying insulin action, and suggests that some human breast cancer may show growth regulation by insulin.
类固醇和肽类激素在人类乳腺癌中的作用机制尚不清楚。我们之前已对一种长期组织培养的人类乳腺癌细胞系进行了表征,该细胞系具有多种类固醇激素受体及反应,为研究类固醇激素作用提供了一个模型。目前的研究描述了一种体外培养的人类乳腺癌,它对生理浓度的胰岛素有反应,表现为大分子合成速率和生长速率增加。在无血清培养基中,10(-11) M的胰岛素可刺激细胞掺入胸苷和尿苷,在10(-8) M时达到最大值。5×10(-11) M的胰岛素可刺激亮氨酸掺入,在10(-9) M时达到最大值。尿苷和亮氨酸掺入的显著刺激在3小时时明显,10小时时达到最大值。胰岛素刺激胸苷掺入存在10小时的延迟期,在14至24小时时达到最大值。24小时后,10(-8) M胰岛素对大分子合成的作用伴随着细胞数量比对照增加69%。在无葡萄糖培养基中也观察到了对大分子合成的作用。胰岛素对蛋白质合成的作用不会被放线菌素D抑制RNA合成所阻断。糖皮质激素部分抑制胰岛素在这些细胞中的作用。该系统为研究胰岛素作用提供了一个模型,并表明一些人类乳腺癌可能受胰岛素的生长调节。