Description:
<jats:title>Abstract</jats:title><jats:p>The over‐expression of the proto‐oncogene HER‐2 (c‐<jats:italic>erb</jats:italic> B‐2/ <jats:italic>neu</jats:italic>) in ovarian, endometrial and mammary carcinoma is an important indicator for poor prognosis. We have previously shown in 3 out of 4 ovarian carcinoma cell lines an interferon‐gamma (IFN‐γ)‐mediated reduction in HER‐2 specific protein and RNA levels. The oncogene expression was lowered only in the ovarian carcinoma cell lines but not in 3 IFN‐γ‐sensitive human breast cancer cell lines. We extended our observations also to IFN type I, α and ω. The expression of the oncogene was measured by both the p185<jats:sup>HER‐2</jats:sup> ELISA and in selected cases by a living cell radioimmunoassay using the monoclonal antibody (MAb) 4D5 against the extracellular domain. Both IFN types reduced the expression of HER‐2 in the ovarian carcinoma cell lines OVCAR‐3, HTB‐77, 2774 and SKOV‐6, and in the SKUT‐2 endometrial carcinoma cells. In contrast, SKOV‐8 human ovarian carcinoma cells were sensitive for both IFN types regarding proliferation, but only IFN‐γ reduced proto‐oncogene expression. In the SKBR‐3 human mammary carcinoma cells, neither IFN type had an effect on HER‐2 expression. The antibodies 4D5, 7C2, 3E8, and 3H4 which bind to the extracellular domain of p185<jats:sup>HER‐2</jats:sup> protein specifically inhibited anchorage‐independent growth of SKBR‐3 and HTB‐77 cells. Expression of the oncogene HER‐2 is the leading prognostic factor in ovarian cancer. Its modulation might represent a mechanism by which IFNs inhibit cell proliferation.</jats:p>