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Epidermal growth factor reduces HER‐2 protein level in human ovarian carcinoma cells
Author(s) -
Marth Christian,
Lang Thomas,
Cronauer Marcus V.,
Doppler Wolfgang,
Zeimet Alain G.,
Bachmair Franz,
Ullrich Axel,
Daxenbichler Günter
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910520226
Subject(s) - epidermal growth factor , ovarian carcinoma , cell culture , growth factor , biology , endocrinology , oncogene , cancer research , medicine , receptor , stimulation , cell , ovarian cancer , cell cycle , cancer , biochemistry , genetics
Over‐expression of the proto‐oncogene HER‐2 (c‐erbB‐2/neu) in ovarian, endometrial, and mammary carcinoma is an indicator of poor prognosis. Interactions between the epidermal growth factor (EGF) receptor and the HER‐2 protein have been described. The aim of this study was to elucidate the effects of EGF on HER‐2 expression. In the human ovarian carcinoma cell lines HTB‐77, OVCAR‐3, 2780, SKOV‐6, SKOV‐8 and 2774, and the human mammary tumor cell line SKBR‐3, total cellular p185 HER‐2 was determined by an ELISA, whereas the surface p185 HER‐2 was measured with a living‐cell RIA. Stimulation of these cell lines with either EGF (0.1–30 nM) or TGF‐α (0.1–30 nM) led to a significant reduction in p185 HER‐2 expression. The effect was more pronounced in cells with normal HER‐2 expression. A reduction of mRNA levels for p185 HER‐2 by EGF was observed in OVCAR‐3 cells but not in the over‐expressing lines HTB‐77 and SKBR‐3. Interestingly, the EGF‐induced effect was not always associated with growth stimulation and was not correlated with the number of EGF binding sites detected by a radioligand assay. Our data indicate that EGF treatment results in a down‐regulation of p185 HER‐2 . © 1992 Wiley‐Liss, Inc.