Expression of c-erbB-41HER4 Is Regulated in T47D Breast Carcinoma Cells by Retinoids and Vitamin D31

Abstract Nuclear steroidlretinoid 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 acidmediated growth inhibition is accompanied with reduced expression of c-erbB-4EIER4 in T47D breast cancer cells as determined by FACS, Western, and RTPCR. 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 D 3 (D 3 ), 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 D 3 represents a highly efficient inducer of c-erbB-4 expression without affecting cell proliferation. © 1999 Academic Press