Gene expression changes triggered by adiponectin in human mammary epithelial and breast cancer cells

Serum levels of adiponectin are inversely associated with breast cancer risk. Adiponectin is reported to exert direct antitumoral effects by inhibition of cell proliferation and increase of apoptosis of breast cancer cells.

We examined molecular mechanisms underlying the antitumoral action of adiponectin. For this purpose, we studied the effect of adiponectin on gene expression in a breast cancer cell line and a non-tumorigenic human mammary epithelial cell line. MCF–7 breast cancer cells and MCF–10A immortalized mammary epithelial cells were treated with adiponectin (10µg/ml) for 48h. Adiponectin effect on gene expression was analyzed by means of DNA microarrays and the data was confirmed by real time RT-PCR analysis of expression of estrogen receptor (ER) α, ERβ1, ERβ2, ERβ5, caspase 1, TR2 orphan nuclear hormone receptor, adiponectin receptor 1 and ubiquitin specific peptidase. Treatment with adiponectin reduced cell growth of MCF–10A mammary epithelial cells, but not of MCF–7 breast cancer cells. In MCF–7 breast cancer cells about 6-fold increased ERβ2 transcript levels were observed, whereas no effect in regulation of other analyzed genes was detected. In contrast, in MCF–10A mammary epithelial cells adiponectin upregulated mRNA levels of ERβ2 and USP more than 5-fold and transcript levels of ERβ5, caspase 1 and TR2 were elevated about 2-fold. These findings suggest that adiponectin has different effects on breast cancer and mammary epithelial cells. Upregulation of ERβ isoforms and caspase 1 which both are known to affect growth or apoptosis of breast cancer cells could be at least one molecular mechanism underlying the antitumoral action of adiponectin.

Funded by ReForM C.

adiponectin - breast cancer cell lines - estrogen receptor - gene regulation