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 breast cancer cells induced rapid growth of ER-positive MCF-7 breast cancer cells with a stimulatory effect observed at 10(-11)M. This heregulin down-regulated the message for ER in MCF-7 cells within 24 hours after stimulation. Similarly the ER protein was down-regulated within 24 to 48 hours after stimulation of cells. However, this down-regulation occurred without activation of the ER, since the progesterone receptor (PR) level of cells stimulated with the 52 kDa heregulin did not increase over the time period measured. As a control, estradiol down-regulated and activated ER as shown by a pronounced increase in PR content of MCF-7 cells. This finding indicates an important role of this heregulin in the down-regulation of ER in estrogen-dependent human breast cancer cells.
Mueller
H
H
Department of Research, University Clinics Medical School, Basel, Switzerland.
Kueng
W
W
Schoumacher
F
F
Herzer
S
S
Eppenberger
U
U
D001943:Breast Neoplasms / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D016762:Genes, fos; D016259:Genes, myc; D006023:Glycoproteins / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D020890:Neuregulin-1; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D006023:Glycoproteins; D006133:Growth Substances; D020890:Neuregulin-1; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone