Zinc-α2-glycoprotein: a proliferative factor for breast cancer? In vitro study and molecular mechanisms.

Zinc-alpha 2-glycoprotein (ZAG) is a new adipokine whose gene expression is downregulated in obese patients. We recently reported ZAG expression in breast tumor or healthy breast tissue and detected this expression at high levels in ductal carcinoma and in normal epithelial adjacent tissue but not in normal tissue of healthy women. In the present study, we used two human breast tumor cell lines (MCF-7 and MDA-MB-231) and one fibrocystic breast cell line (MCF-10a) to examine whether recombinant ZAG has an effect on proliferative/apoptotic response in breast cancer cell lines. ZAG seemed to exert a proliferative effect on breast cancer cell proliferation [+11 to 27% in MCF-7 with (ZAG) = 5-20 mu g/ml; +13% in MDA-MB-231 with (ZAG) = 5 mu g/ml] and, on the contrary, an anti-proliferative effect in the fibrocystic breast cell line [-5 to -8% in MCF-10a with (ZAG) = 5-10 mu g/ml]. ZAG was able to modulate gene and protein expression involved in the apoptotic response. However, further studies are required to fully elucidate the effects of ZAG on the proliferation of mammary cells.