UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker.
Mucin O-glycosylation is characterized in cancer by aberrant expression of immature carbohydrate structures (Tn, T, and sialyl-Tn antigens). The UDP-N-acetyl-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-T) family enzymes regulate the initial steps of mucin O-glycosylation and could be responsible for the altered glycosylation observed in cancer. Considering that we recently found the ppGalNAc-T6 mRNA expressed in breast carcinomas, we produced a highly specific monoclonal antibody (MAb T6.3) to assess the expression profile of ppGalNAc-T6 protein product in breast tissues. The expression of ppGalNAc-T6 by breast carcinoma cells was confirmed on MCF-7 and T47D cell lines. In formalin-fixed tissues, ppGalNAc-T6 expression was observed in 60/74 (81%) breast cancers, 21/23 (91.3%) adjacent ductal carcinoma in situ (DCIS), 4/20 benign breast lesions (2/2 sclerosing adenosis and 2/13 fibroadenoma), and in 0/5 normal breast samples. We observed a statistically significant association of ppGalNAc-T6 expression with T1 tumor stage. This fact, as well as the observation that ppGalNAc-T6 was strongly expressed in sclerosing adenosis and in most DCIS, suggests that ppGalNAc-T6 expression could be an early event during human breast carcinogenesis. Considering that an abnormal O-glycosylation greatly contributes to the phenotype and biology of breast cancer cells, ppGalNAc-T6 expression could provide new insights about breast cancer glycobiology.
Berois
Nora
N
Departamento de Bioquímica, Laboratorio de Oncología Básica, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Mazal
Daniel
D
Ubillos
Luis
L
Trajtenberg
Felipe
F
Nicolas
André
A
Sastre-Garau
Xavier
X
Magdelenat
Henri
H
Osinaga
Eduardo
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001941:Breast Diseases / Q000201:enzymology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology; D018275:Carcinoma, Lobular / Q000201:enzymology; D002291:Carcinoma, Papillary / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D042361:Mammary Glands, Human / Q000201:enzymology; D008679:Metaplasia; D051379:Mice; D008875:Middle Aged; D017350:N-Acetylgalactosaminyltransferases / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D017350:N-Acetylgalactosaminyltransferases; C121529:UDP-N-acetylgalactosamine polypeptide N-acetylgalactosaminyltransferase 6