Modulation of estrogen receptor and epidermal growth factor receptor mRNAs by phorbol ester in MCF 7 breast cancer cells.

Previous studies have demonstrated an inverse relationship between estrogen receptor (ER) and epidermal growth factor receptor (EGF-R) gene expression in human breast cancer cells. This relationship was further investigated in MCF 7 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA). Exposure to 10 nM TPA resulted in a time-dependent increase in EGF-R mRNA, first apparent at 3 h and maximal between 9 and 24 h. There was a concomitant fall in ER mRNA with a maximum decline to 15-20% of control between 12 and 24 h. Although EGF-R mRNA levels declined between 24 and 72 h, both EGF-R mRNA and EGF-R binding remained above control levels and this was accompanied by a sustained depression of ER mRNA. These data support the view that ER and EGR-R gene expression is inversely regulated in human breast cancer and describe for the first time an inhibitory effect of a phorbol ester on steroid hormone receptor gene expression.