Effects of interferons on the expression of the proto-oncogene her-2 in human ovarian carcinoma cells

✍ Scribed by Christian Marth; Marcus V. Cronauer; Wolfgang Doppler; Dietmar Öfner; Axel Ullrich; Günter Daxenbichler

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: French
• Weight: 580 KB
• Volume: 50
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910500114

✦ Synopsis

The over-expression of the proto-oncogene HER-2 (c-erbB-2/ neu) 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 interferongamma (IFN-+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-y-sensitive human breast cancer cell lines. We extended our observations also to IFN type I, a and w. The expression of the oncogene was measured by both the p 185HER-' 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-y 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 p I 85HER-2 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.