Epidermal growth factor reduces HER-2 protein level in human ovarian carcinoma cells.
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 p185HER-2 was determined by an ELISA, whereas the surface p185HER-2 was measured with a living-cell RIA. Stimulation of these cell lines with either EGF (0.1-30 nM) or TGF-alpha (0.1-30 nM) led to a significant reduction in p185HER-2 expression. The effect was more pronounced in cells with normal HER-2 expression. A reduction of mRNA levels for p185HER-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 p185HER-2.
Department of Obstetrics and Gynecology, Innsbruck University Clinic, Austria.
C
C
Marth
T
T
Lang
M V
MV
Cronauer
W
W
Doppler
A G
AG
Zeimet
F
F
Bachmair
A
A
Ullrich
G
G
Daxenbichler
D001483:Base Sequence; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha; C000715470:MAS1 protein, human