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

Int J Cancer. 1998 Sep 11;77(6):937-41. doi: 10.1002/(sici)1097-0215(19980911)77:6<937::aid-ijc24>;2-x.


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 gamma-interferon of carcinoma cells cultured in vitro induced a strong reexpression 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • DNA Primers
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Interferon-gamma / pharmacokinetics*
  • Major Histocompatibility Complex / genetics*
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism*
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Transgenic
  • Polymerase Chain Reaction
  • Receptor, ErbB-2 / metabolism*


  • DNA Primers
  • Interferon-gamma
  • Receptor, ErbB-2