ESTROGEN AND EPIDERMAL GROWTH-FACTOR DOWN-REGULATE ERBB-2 ONCOGENE PROTEIN EXPRESSION IN BREAST-CANCER CELLS BY DIFFERENT MECHANISMS

被引:34
作者
ANTONIOTTI, S
TAVERNA, D
MAGGIORA, P
SAPEI, ML
HYNES, NE
DEBORTOLI, M
机构
[1] UNIV TURIN,DEPT ANIM BIOL,MOLEC CELL BIOL LAB,I-10123 TURIN,ITALY
[2] FRIEDRICH MIESCHER INST,CH-4002 BASEL,SWITZERLAND
关键词
D O I
10.1038/bjc.1994.454
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Mitogen-induced mammary cell growth is often accompanied by decreased levels of expression of the p185(erbB-2) protein. We have previously reported that oestrogen inhibits erbB-2 mRNA and protein expression in breast cancer cells, while epidermal growth factor (EGF) treatment has been shown to decrease p185(erbB-2) levels in normal mouse mammary epithelial cells. In the present work, we studied the effect of oestrogen and EGF on erbB-2 expression in oestrogen-responsive breast cancer cells. We observed that both oestrogen and EGF comparably down-regulated p185(erbB-2) levels, while stimulating growth of T47D and ZR75.1 cells. Oestrogens, but not EGF, concomitantly down-regulated erbB-2 mRNA. Run-on analysis showed a reduced erbB-2 transcription rate in the presence of oestrogens. Furthermore, the transcriptional activity of a 219 bp proximal fragment of the human erbB-2 promoter was repressed by oestrogens, whereas if was enhanced by EGF. EGF stimulated both tyrosine phosphorylation and autokinase activity of p185(erbB-2) We conclude that oestrogens, but not EGF, inhibit erbB-2 expression by transcriptional repression, while EGF down-regulates p185(erbB-2) at a post-translational level. Thus, two factors converging in terms of effects on cell growth, display divergent mechanisms of regulation of erbB-2 expression.
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页码:1095 / 1101
页数:7
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