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Gamma-interferon reduces expression of the protooncogene c-erbB-2 in human ovarian carcinoma cells
C Marth1, E Müller-Holzner, E Greiter
1Department of Obstetrics and Gynecology, Innsbruck University Clinic, Austria.
Abstract:
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.
Insights
Gamma-interferon reduces c-erbB-2 (HER-2/neu) protein in ovarian carcinoma cells, correlating with antiproliferative effects. This modulation offers a potential therapeutic strategy for ovarian cancer.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Protooncogene c-erbB-2 (HER-2/neu) overexpression is linked to poor prognosis in ovarian and mammary carcinoma.
- c-erbB-2 expression levels are a key prognostic factor in ovarian cancer.
Purpose of the Study:
- To investigate the effect of gamma-interferon on c-erbB-2 expression in ovarian carcinoma cell lines.
- To determine if gamma-interferon-mediated reduction in c-erbB-2 correlates with antiproliferative activity.
Main Methods:
- Treatment of ovarian carcinoma cell lines with gamma-interferon.
- Assessment of c-erbB-2 protein levels.
- Evaluation of cell proliferation inhibition.
Main Results:
- Gamma-interferon reduced c-erbB-2 specific protein in three of four ovarian carcinoma cell lines.
- This reduction correlated with antiproliferative action.
- No correlation was found between absolute c-erbB-2 levels and sensitivity to gamma-interferon's antiproliferative effects.
- Other chemotherapeutic agents inhibited proliferation but did not affect c-erbB-2 expression.
- c-erbB-2 expression was not lowered in gamma-interferon-sensitive breast cancer cell lines.
Conclusions:
- Gamma-interferon can modulate c-erbB-2 oncogene expression in ovarian carcinoma.
- This modulation may be a mechanism by which gamma-interferon exerts its antiproliferative effects.
- Targeting c-erbB-2 expression could be a therapeutic avenue for ovarian cancer.