Down regulation of major histocompatibility complex class I expression in mammary carcinoma of HER-2/neu transgenic mice

✍ Scribed by Pier-Luigi Lollini; Giordano Nicoletti; Lorena Landuzzi; Carla De Giovanni; Ilaria Rossi; Emma Di Carlo; Piero Musiani; William J. Muller; Patrizia Nanni

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: French
• Weight: 205 KB
• Volume: 77
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19980911)77:6<937::aid-ijc24>3.0.co;2-x

✦ Synopsis

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-2 q ) 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 ␥-interferon of carcinoma cells cultured in vitro induced a strong reexpression of H-2 q 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.