Gamma-interferon reduces expression of the protooncogene c-erbB-2 in human ovarian carcinoma cells.
The overexpression of the protooncogene c-erbB-2 (HER-2/neu) in ovarian and mammary carcinoma is an important indicator for a bad prognosis. In this study we demonstrate that, in three of four ovarian carcinoma cell lines, there is a gamma-interferon-mediated reduction in c-erbB-2 specific protein, and this effect was found to correlate with the antiproliferative action. It is interesting to note that there is no relation between the absolute amount of c-erbB-2 protein expressed and the sensitivity of the ovarian carcinoma cells for an antiproliferative activity of gamma-interferon. Other chemotherapeutic agents did not affect c-erbB-2 expression, although they inhibited the proliferation. The oncogene expression was lowered only in the ovarian carcinoma cell lines and not in three gamma-interferon-sensitive human breast cancer cell lines. Expression of the oncogene c-erbB-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which gamma-interferon inhibits cell proliferation.
Marth
C
C
Department of Obstetrics and Gynecology, Innsbruck University Clinic, Austria.
Müller-Holzner
E
E
Greiter
E
E
Cronauer
M V
MV
Zeimet
A G
AG
Doppler
W
W
Eibl
B
B
Hynes
N E
NE
Daxenbichler
G
G
D002277:Carcinoma / Q000235:genetics* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011519:Proto-Oncogenes / Q000235:genetics*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D009363:Neoplasm Proteins; D007371:Interferon-gamma