Prevention of breast tumour development in vivo by downregulation of the p185neu receptor.
Certain strains of transgenic mice that express the rat neu oncogene (neuT) in mammary epithelial cells develop breast tumours at an average of 44 weeks of age. In this study, intraperitoneal injection of a monoclonal anti-receptor antibody specific for the rat neuT oncogene product dramatically affected tumour development in these transgenic mice in a dose-dependent manner. A significant proportion (50%) of mice, when injected with anti-receptor antibodies, did not develop tumours even after 90 weeks of age. The phosphotyrosine levels of the membrane fraction of breast tissues in the anti-receptor antibody-treated mice were almost completely abolished when a higher dose of antibodies was used. This study demonstrates, for the first time, that immunologic manipulation of an oncogene product can effectively prevent the development of tumours in a rodent transgenic model.
Katsumata
M
M
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104, USA.
Okudaira
T
T
Samanta
A
A
Clark
D P
DP
Drebin
J A
JA
Jolicoeur
P
P
Greene
M I
MI
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D000912:Antibodies, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D004306:Dose-Response Relationship, Immunologic; D015972:Gene Expression Regulation, Neoplastic; D005813:Genes, Synthetic; D006801:Humans; D007116:Immunization, Passive; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000517:prevention & control*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D019076:Transgenes
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D009363:Neoplasm Proteins; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011993:Recombinant Fusion Proteins