López-Boado Y S, Díez-Itza I, Tolivia J, López-Otín C
Departamento de Biología Funcional, Universidad de Oviedo, Spain.
Breast Cancer Res Treat. 1994;29(3):247-58. doi: 10.1007/BF00666478.
We have studied the hormonal regulation of the gene encoding Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a human protein with a high degree of amino acid sequence similarity to class I histocompatibility antigens that is produced by a specific subset of breast carcinomas. Northern blot analysis revealed that dexamethasone and 5 alpha-dihydrotestosterone strongly induced the accumulation of Zn-alpha 2-gp mRNA in T-47D human breast cancer cells. Furthermore, the effect of these two hormones was shown to be additive, since the combination of both hormones produced a stimulation of Zn-alpha 2-gp mRNA of at least 3-fold over that produced by either hormone alone. By contrast, the addition of 5 beta-dihydrotestosterone, 17 beta-estradiol, or progesterone failed to induce the expression of Zn-alpha 2-gp. The stimulatory effect of glucocorticoids and androgens on Zn-alpha 2-gp expression was produced in a time and dose dependent manner, without significantly affecting the cell proliferation rate. A time-course study demonstrated that the induction of Zn-alpha 2-gp mRNA by androgens and glucocorticoids reached a level of 4 or 3.2-fold over the untreated control after seven days of incubation in the presence of a 10(-7) M concentration of 5 alpha-dihydrotestosterone or dexamethasone, respectively. A dose-response study showed that as little as 10(-11) M of 5 alpha-dihydrotestosterone or dexamethasone produced an accumulation of Zn-alpha 2-gp mRNA of 2.4 or 2.1-fold over the control, respectively. On the basis of these results, we propose that Zn-alpha2-gp may be useful as a biochemical marker of breast carcinomas with a specific pattern of hormone responsiveness in whose development glucocorticoids and/or androgens may play a significant role.
我们研究了锌α2-糖蛋白（Zn-α2-gp）编码基因的激素调节，Zn-α2-gp是一种人类蛋白质，其氨基酸序列与I类组织相容性抗原高度相似，由特定的乳腺癌子集产生。Northern印迹分析显示，地塞米松和5α-二氢睾酮强烈诱导T-47D人乳腺癌细胞中Zn-α2-gp mRNA的积累。此外，这两种激素的作用是相加的，因为两种激素联合使用对Zn-α2-gp mRNA的刺激作用比单独使用任何一种激素产生的刺激作用至少高3倍。相比之下，添加5β-二氢睾酮、17β-雌二醇或孕酮未能诱导Zn-α2-gp的表达。糖皮质激素和雄激素对Zn-α2-gp表达的刺激作用呈时间和剂量依赖性，且对细胞增殖率无显著影响。一项时间进程研究表明，在10^(-7)M浓度的5α-二氢睾酮或地塞米松存在下孵育7天后，雄激素和糖皮质激素诱导的Zn-α2-gp mRNA水平分别比未处理对照高4倍或3.2倍。剂量反应研究表明，低至10^(-11)M的5α-二氢睾酮或地塞米松分别使Zn-α2-gp mRNA的积累量比对照高2.4倍或2.1倍。基于这些结果，我们提出Zn-α2-gp可能作为具有特定激素反应模式的乳腺癌的生化标志物，在其发展过程中糖皮质激素和/或雄激素可能起重要作用。
