Hormonal modulation of HER-2/neu protooncogene messenger ribonucleic acid and p185 protein expression in human breast cancer cell lines.
Hormonal modulation of HER-2/neu protooncogene messenger ribonucleic acid and p185 protein expression in human breast cancer cell lines.
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发表时间：
1990-07
期刊：
影响因子：
11.2
通讯作者：
L. D. Read;D. Keith;D. Slamon;B. Katzenellenbogen
中科院分区：
文献类型：
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作者：
L. D. Read;D. Keith;D. Slamon;B. Katzenellenbogen
最近的研究表明，HER-2/neu原癌基因的过度表达可能在一些乳腺肿瘤的侵袭性临床行为中发挥作用。由于激素也被称为改变这些细胞的增殖速率和侵袭性，我们已经研究了性类固醇激素和抗激素的HER-2/neu mRNA和蛋白质的水平在人乳腺癌细胞系使用互补DNA和抗体探针的影响。在含有高水平雌激素受体和雌二醇（E2）诱导的孕酮受体（PR）的MCF-7细胞中，1 nM E2导致HER-2/neu mRNA（4.8个酶）快速下降，6 h时降至对照值的40%，HER-2/neu蛋白质逐渐下降，24 h时降至50%。HER-2/neu蛋白和mRNA水平在E2治疗的1周内保持降低。E2的作用是剂量依赖性的，在10（-10）M E2及以上的浓度下观察到最大作用，并且抗雌激素部分逆转E2诱导的HER-2/neu表达的降低。这些特征表明，观察到的HER-2/neu的调节是雌激素受体介导的过程。相比之下，孕激素没有改变E2引发的含有高水平PR的MCF-7细胞中HER-2/neu mRNA或蛋白质水平;在含有低水平ER和高水平PR的T47 D细胞中，添加E2或胱抑素R5020或抗胱抑素RU 38，486在6天的处理中对HER-2/neu mRNA或蛋白质水平没有显著影响。这些结果表明，雌激素，而不是resistin调节HER-2/neu原癌基因在这些乳腺癌细胞系的表达，并建议与高水平的HER-2/neu mRNA和蛋白质的侵略性可能是解耦的雌激素刺激的增殖在这些细胞。
Recent work has suggested that overexpression of the HER-2/neu protooncogene may play a role in the aggressive clinical behavior of some breast tumors. Since hormones are also known to change the proliferation rate and invasiveness of these cells, we have studied the effect of sex steroid hormones and antihormones on levels of the HER-2/neu mRNA and protein in human breast cancer cell lines using complementary DNA and antibody probes. In MCF-7 cells, which contain high levels of estrogen receptor and an estradiol (E2)-inducible progesterone receptor (PR), 1 nM E2 caused a rapid drop in HER-2/neu mRNA (4.8 kilobases), to 40% of control values by 6 h, and a more gradual decrease in HER-2/neu protein, to 50% by 24 h. HER-2/neu protein and mRNA levels remained reduced throughout 1 week of E2 treatment. The effect of E2 was dose dependent, with the maximal effect seen with concentrations of 10(-10) M E2 and above, and antiestrogen partly reversed the E2-induced decrease in HER-2/neu expression. These characteristics suggest that the observed modulation of HER-2/neu is an estrogen receptor-mediated process. In contrast, progestins did not change HER-2/neu mRNA or protein levels in E2-primed MCF-7 cells that contain high levels of PR; in T47D cells, which contain low levels of ER and high levels of PR, addition of E2 or the progestin R5020 or the antiprogestin RU38,486 had no significant effect on HER-2/neu mRNA or protein levels over 6 days of treatment. These results indicate that estrogen but not progestin modulates HER-2/neu protooncogene expression in these breast cancer cell lines and suggest that aggressiveness associated with high levels of HER-2/neu mRNA and protein may be uncoupled from estrogen-stimulated proliferation in these cells.