Tn antigen is a pre-cancerous biomarker in breast tissue and serum in n-nitrosomethylurea-induced rat mammary carcinogenesis
Alvaro Babino
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorPablo Oppezzo
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorStella Bianco
Pathological Anatomy Department, Clinical Hospital, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorEnrique Barrios
Biophysics Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorNora Berois
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorHéctor Navarrete
Pathological Anatomy Department, Clinical Hospital, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorCorresponding Author
Eduardo Osinaga
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Laboratorio de Oncología Básica, Depto. de Bioquímica, Facultad de Medicina, Av. Gral. Flores 2125, Montevideo CP 11800, Uruguay. Fax: (598 2) 924 95 63Search for more papers by this authorAlvaro Babino
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorPablo Oppezzo
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorStella Bianco
Pathological Anatomy Department, Clinical Hospital, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorEnrique Barrios
Biophysics Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorNora Berois
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorHéctor Navarrete
Pathological Anatomy Department, Clinical Hospital, Faculty of Medicine, Montevideo, Uruguay
Search for more papers by this authorCorresponding Author
Eduardo Osinaga
Basic Oncology Laboratory, Biochemistry Department, Faculty of Medicine, Montevideo, Uruguay
Laboratorio de Oncología Básica, Depto. de Bioquímica, Facultad de Medicina, Av. Gral. Flores 2125, Montevideo CP 11800, Uruguay. Fax: (598 2) 924 95 63Search for more papers by this authorAbstract
The Tn determinant (GalNAcα-O-Ser/Thr), normally a cryptic structure in mucin-type O-glycans, is a tumor-associated marker which has attracted particular interest in cancer biology. We herein report the characterization of N-nitrosomethylurea (NMU)-induced breast cancer in rats as a new model for the study of aberrant O-glycosylation products. Tn-antigen expression is detectable not only in mammary carcinoma induced by NMU but also in carcinogen-initiated mammary epithelium, indicating that Tn could be a pre-cancerous biomarker in rats treated with NMU. Serum Tn levels were followed up longitudinally in 30 rats from the time of the first injection of NMU to the development of advanced breast cancer. Tn antigen increased in serum several weeks before tumor development, and became highly positive after 56 days of carcinogenesis (prior to breast-cancer occurrence), and the levels correlated with Tn expression in mammary tissues. However, during the follow-up after detection of mammary cancer, all animals displayed a significant decrease of serum Tn antigen, and low levels were observed in animals with advanced breast cancer. We have shown that the humoral immune response to cancer, with the production of anti-Tn antibodies, could hamper the detection of Tn antigen in animals with advanced breast cancer. These results suggest that NMU-induced rat mammary carcinogenesis is a useful experimental model to study the regulation of O-glycosylation at the cellular level during malignant transformation. Int. J. Cancer 86:753–759, 2000. © 2000 Wiley-Liss, Inc.
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