Expression of c-erbB-4/HER4 is regulated in T47D breast carcinoma cells byretinoids and vitamin D-3

Nuclear steroid/retinoid and membrane c-erbB receptor tyrosine kinase signa ling control proliferation and differentiation of mammary epithelial cells, Recently, we reported that retinoic acids are efficient repressors of c-er bB-2 and -3, but not of c-erbB-1 gene expression, Here we demonstrate that retinoic acid-mediated growth inhibition is accompanied with reduced expres sion of c-erbB-4/HER4 in T47D breast cancer cells as determined by FAGS, We stern, and RT-PCR. AU-trans and 9-cis retinoic acid reduce c-erbB-4 express ion to 30%-60% of control, depending on the concentration. Dexamethasone (D ex) is inactive on T47D cell growth and on c-erbB-4 expression. Vitamin D-3 (D-3), in contrast, acts as a strong inducer, elevating c-erbB-4 expressio n up to 360% at the protein level and more than twofold at the mRNA, but do es not significantly affect cell growth. We conclude that retinoic acids ar e efficient growth inhibitors and repressors of c-erbB-4 gene expression, D ex is unable to influence cell growth and c-erbB-4, whereas D-3 represents a highly efficient inducer of c-erbB-4 expression without affecting cell pr oliferation, (C) 1999 Academic Press.