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[Interferon-gamma suppresses expression of the HER-2 oncogene in ovarian cancer cells]
C Marth1, E Müller-Holzner, A G Zeimet
1Universitätsklinik für Frauenheilkunde, Innsbruck Osterreich.
Abstract:
The overexpression of the proto-oncogene HER-2 (c-erbB-2/neu) in ovarian and mammary carcinoma is an important indicator for a bad prognosis. In this study we demonstrate that in 7 out of 8 ovarian carcinoma cell lines there is an interferon-gamma-mediated reduction in HER-2 specific protein, and this effect was found to correlate with the antiproliferative action. It is interesting to note that there is no relationship between the absolute amount of HER-2 protein expressed and the sensitivity of the ovarian carcinoma cells for an antiproliferative activity of interferon-gamma. Other chemotherapeutic agents did not affect HER-2 expression although they inhibited the proliferation. The oncogene expression was lowered only in the ovarian carcinoma cell lines and not in 3 interferon-gamma sensitive human breast cancer cell lines. Expression of the oncogene HER-2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which interferon-gamma inhibits cell proliferation.
Insights
Interferon-gamma reduces HER-2 protein in ovarian cancer cells, correlating with reduced proliferation. This HER-2 modulation by interferon-gamma may explain its antiproliferative effects in ovarian carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Proto-oncogene HER-2 (c-erbB-2/neu) overexpression is linked to poor prognosis in ovarian and mammary carcinoma.
- HER-2 expression levels are a key prognostic factor in ovarian cancer.
Purpose of the Study:
- To investigate the effect of interferon-gamma on HER-2 expression in ovarian carcinoma cell lines.
- To determine if HER-2 modulation by interferon-gamma correlates with its antiproliferative activity.
Main Methods:
- Treatment of ovarian and breast carcinoma cell lines with interferon-gamma.
- Assessment of HER-2 specific protein levels.
- Evaluation of antiproliferative effects of interferon-gamma and other chemotherapeutic agents.
Main Results:
- Interferon-gamma reduced HER-2 protein in 7 out of 8 ovarian carcinoma cell lines.
- The reduction in HER-2 protein correlated with antiproliferative action.
- No direct relationship was found between absolute HER-2 levels and sensitivity to interferon-gamma's antiproliferative effects.
- Interferon-gamma did not affect HER-2 expression in sensitive breast cancer cell lines.
- Other chemotherapeutic agents inhibited proliferation but not HER-2 expression.
Conclusions:
- Interferon-gamma effectively reduces HER-2 oncogene expression in ovarian carcinoma.
- HER-2 modulation by interferon-gamma is a potential mechanism for its antiproliferative effects in ovarian cancer.
- Interferon-gamma's impact on HER-2 is specific to ovarian carcinoma cell lines in this study.