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‐specific transcriptional control of a mammary tumor virus long terminal repeat (Tg‐MMTVneu mice) spontaneously develop mammary carcinomas. HER‐2/neu is a tumor antigen that can be recognized by cytotoxic T lymphocytes if tumor cells present the appropriate major histocompatibility complex (MHC) class I glycoproteins. The purpose of this work was to assess whether mammary carcinomas arising in Tg‐MMTVneu mice correctly expressed MHC (H‐2q) class I gene products. We analyzed by flow cytometry 51 primary tumors from 19 transgenic mice. About one‐half of the tumors showed a reduced expression of class I antigens. All tumors were highly positive for membrane neu. Some mice had multiple mammary carcinomas with widely different MHC expression levels, and most mice had at least one tumor with a low expression. Treatment with γ‐interferon of carcinoma cells cultured in vitro induced a strong re‐expression of H‐2q antigens. Our results suggest that the immune response activated 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 products. Int. J. Cancer 77:937–941, 1998.© 1998 Wiley‐Liss, Inc.