M. Offterdinger et al., RETINOIDS CONTROL THE EXPRESSION OF C-ERBB RECEPTORS IN BREAST-CANCERCELLS, Biochemical and biophysical research communications (Print), 251(3), 1998, pp. 907-913
Nuclear retinoid and membrane c-erbB receptors participate in signal t
ransduction systems that control mammary epithelial cell proliferation
and differentiation. Recently, we demonstrated that c-erbB receptor a
ctivation stimulates retinoic acid receptor-a expression. We now repor
t that retinoids reduce SKBR-3 breast cancer cell growth by inhibiting
the cell cycle and by inducing apoptosis. This is accompanied with re
duced c-erbB expression as determined by FAGS, Western, Northern, RT-P
CR, and reporter assays. All-trans (ATRA) and g-cis retinoic acid (9cR
A) reduce c-erbB-1 protein to 50-100%, c-erbB-2 to 20-30%, and c-erbB-
3 to 10-50% of control, depending on the concentration, respectively,
without influencing the tyrosine phosphorylation status. Down-regulati
on of c-erbB-2 and -3 was seen at all levels analyzed, whereas c-erbB-
1 mRNA remained unchanged. Retinoic acid-mediated down-regulation of g
rowth and c-erbB-2 and -3 expression was also seen in MCF-7 cells. We
conclude that retinoic acids are efficient repressors of c-erbB-2 and
-3 gene expression, whereas c-erbB-1 is not markedly affected. (C) 199
8 Academic Press.