Expression of c-erbB-4/HER4 is regulated in T47D breast carcinoma cells by retinoids and vitamin D3
Offterdinger, M.; Schneider, S.M.; Huber, H.; Grunt, T.W.
Biochemical and Biophysical Research Communications 258(3): 559-564
1999
ISSN/ISBN: 0006-291X PMID: 10383375 Document Number: 508518
Nuclear steroid/retinoid and membrane 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 expression. Here we demonstrate that retinoic 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 T47D cell growth and on c-erbB-4 expression. Vitamin D3 (D3), in contrast, acts as a strong inducer, elevating c-erbB-4 expression up to 360% at the protein level and more than twofold at the mRNA, but does not significantly affect cell growth. We conclude that retinoic acids are efficient growth inhibitors and repressors of c-erbB-4 gene expression. Dex is unable to influence cell growth and c-erbB-4, whereas D3 represents a highly efficient inducer of c-erbB-4 expression without affecting cell proliferation.