RETINOIDS CONTROL THE EXPRESSION OF C-ERBB RECEPTORS IN BREAST-CANCERCELLS

Citation
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
Citations number
41
Categorie Soggetti
Biology,Biophysics
ISSN journal
0006291X
Volume
251
Issue
3
Year of publication
1998
Pages
907 - 913
Database
ISI
SICI code
0006-291X(1998)251:3<907:RCTEOC>2.0.ZU;2-O
Abstract
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.