Glucocorticoids and androgens up-regulate the Zn-alpha 2-glycoprotein messenger RNA in human breast cancer cells.
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.
López-Boado
Y S
YS
Departamento de Biología Funcional, Universidad de Oviedo, Spain.
Díez-Itza
I
I
Tolivia
J
J
López-Otín
C
C
D000728:Androgens / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005938:Glucocorticoids / Q000494:pharmacology*; D006023:Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D029589:Seminal Plasma Proteins; D013997:Time Factors; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000090203:Zn-Alpha-2-Glycoprotein
D000728:Androgens; D005938:Glucocorticoids; D006023:Glycoproteins; D012333:RNA, Messenger; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein