SELECTIVE REGULATION OF STEROID-RECEPTOR EXPRESSION IN MCF-7 BREAST-CANCER CELLS BY A NOVEL MEMBER OF THE HEREGULIN FAMILY

A 52 kDa heregulin secreted by estrogen receptor (ER)-negative human b reast cancer cells induced rapid growth of ER-positive MCF-7 breast ca ncer cells with a stimulatory effect observed at 10-(11)M. This heregu lin down-regulated the message for ER in MCF-7 cells within 24 hours a fter stimulation. Similarly the ER protein was down-regulated within 2 4 to 48 hours after stimulation of cells. However, this down-regulatio n occured without activation of the ER, since the progesterone recepto r (PR) level of cells stimulated with the 52 kDa heregulin did not inc rease over the time period measured. As a control, estradiol down-regu lated and activated ER as shown by a pronounced increase in PR content of MCF-7 cells. This finding indicates an important role of this here gulin in the down-regulation of ER in estrogen-dependent human breast cancer cells. (C) 1995 Academic Press, Inc.