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 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.
Institute for Cancer Research, University of Bologna, Italy. pierluigi@lollini.dsnet.it
P L
PL
Lollini
G
G
Nicoletti
L
L
Landuzzi
C
C
De Giovanni
I
I
Rossi
E
E
Di Carlo
P
P
Musiani
W J
WJ
Muller
P
P
Nanni
D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017931:DNA Primers; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000493:pharmacokinetics*; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*
D017931:DNA Primers; D007371:Interferon-gamma; D018719:Erb-b2 Receptor Tyrosine Kinases