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

Pier Luigi Lollini, Giordano Nicoletti, Lorena Landuzzi, Carla De Giovanni, Ilaria Rossi, Emma Di Carlo, Piero Musiani, William J. Muller, Patrizia Nanni

Research output: Contribution to journalArticle

Abstract

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 (H2(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 γ-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.

Original languageEnglish
Pages (from-to)937-941
Number of pages5
JournalInternational Journal of Cancer
Volume77
Issue number6
DOIs
Publication statusPublished - 1998

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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