Expression of c-erbB-4/HER4 is regulated in T47D breast carcinoma cells by retinoids and vitamin D3.
Nuclear steroid/retinoid and memgbrane c-erbB receptor tyrosine kinase signaling control proliferation and differentiation of mammary epithelial cells. Recently, we reported that retinoic acids are efficient repressors of c-erbB-2 and -3, but not of c-erbB-1 gene expresson. Here we demonstrate that retinoid acid- mediated growth inhibition is accompanied with reduced expression of c-erbB-4/HER4 in T47D breast cancer cells as determined by FACS, Western, and RT-PCR. All-trans and 9-cis retinoic acid reduce c-erbB-4 expression to 30%-60% of control, depending on the concentration. Dexamethasone (Dex) is inactive on D3 (D3), in contrast, acts as a strong inducer, elevation more that twofold at the mRNA, but does not significantly affect cell growth. We concolude that retinoic acids are efficient growth inhibitors and repressors of cell growth and c-erbB-4, whereas D3 represents a highly efficient inducer of c-erbB-4 expression with affecting cell proliferation.
Offterdinger
M
M
Laboratory for Cell Growth, Division of Oncology, University of Vienna, Waehringer Guertel 18-20, A-1090, Vienna, Austria.
Schneider
S M
SM
Huber
H
H
Grunt
T W
TW
D001483:Base Sequence; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002762:Cholecalciferol / Q000494:pharmacology*; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics; D066247:Receptor, ErbB-4; D012176:Retinoids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D012333:RNA, Messenger; D012176:Retinoids; D002762:Cholecalciferol; D003907:Dexamethasone; D066246:ErbB Receptors; D066247:Receptor, ErbB-4