DOWN-REGULATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION IN MAMMARY-CARCINOMA OF HER-2 NEU TRANSGENIC MICE/

Transgenic mice carrying the HER-2/neu proto-oncogene under tissue-spe cific transcriptional control of a mammary tumor virus long terminal r epeat (Tg-MMTVneu mice) spontaneously develop mammary carcinomas. HER- 2/neu is a tumor antigen that can be recognized by cytotoxic T lymphoc ytes if tumor cells present the appropriate major histocompatibility c omplex (MHC) class I glycoproteins. The purpose of this work was to as sess whether mammary carcinomas arising in Tg-MMTVneu mice correctly e xpressed MHC (H-2(q)) class I gene products. We analyzed by flow cytom etry 51 primary tumors from 19 transgenic mice. About one-half of the tumors showed a reduced expression of class I antigens. All tumors wer e highly positive for membrane neu. Some mice had multiple mammary car cinomas with widely different MHC expression levels, and most mice had at least one tumor with a low expression. Treatment with gamma-interf eron of carcinoma cells cultured in vitro induced a strong reexpressio n of H-2(q) antigens. Our results suggest that the immune response act ivated in vivo by HER-2/neu-positive tumors can lead to the emergence of escape variants characterized by a down-regulation of MHC class I p roducts. (C) 1998 Wiley-Liss, Inc.