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Glucocorticoids and androgens up-regulate the Zn-α2-glycoprotein messenger RNA in human breast cancer cells

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Summary

We have studied the hormonal regulation of the gene encoding Zn-α2-glycoprotein (Zn-α2-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 5α-dihydrotestosterone strongly induced the accumulation of Zn-α2-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-α2-gp mRNA of at least 3-fold over that produced by either hormone alone. By contrast, the addition of 5β-dihydrotestosterone, 17β-estradiol, or progesterone failed to induce the expression of Zn-α2-gp. The stimulatory effect of glucocorticoids and androgens on Zn-α2-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-α2-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 5α-dihydrotestosterone or dexamethasone, respectively. A dose-response study showed that as little as 10−11 M of 5α-dihydrotestosterone or dexamethasone produced an accumulation of Zn-α2-gp mRNA of 2.4 or 2.1-fold over the control, respectively. On the basis of these results, we propose that Zn-α2-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.

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Authors and Affiliations

  1. Departamento de Biología Funcional, Facultad de Medicina, Universidad de Oviedo, 33006, Oviedo, Spain

    Yolanda S. López-Boado, Irene Díez-Itza & Carlos López-Otín

  2. Servicio de Ginecología, Hospital Carmen y Severo Ochoa, Asturias

    Irene Díez-Itza

  3. Departamento de Morfología y Biología Celular, Universidad de Oviedo, Spain

    Jorge Tolivia

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  1. Yolanda S. López-Boado
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  2. Irene Díez-Itza
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  3. Jorge Tolivia
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  4. Carlos López-Otín
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López-Boado, Y.S., Díez-Itza, I., Tolivia, J. et al. Glucocorticoids and androgens up-regulate the Zn-α2-glycoprotein messenger RNA in human breast cancer cells. Breast Cancer Res Tr 29, 247–258 (1994). https://doi.org/10.1007/BF00666478

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