Zhuang D, Yousefi S, Dennis J W
Samuel Lunenfeld Research Institute, Mt. Sinai Hospital, Toronto, Ontario.
Cancer Biochem Biophys. 1991 Nov;12(3):185-98.
The serine/threonine O-linked carbohydrates GalNAc alpha and Gal beta 1-3GalNAc alpha, referred to as Tn and T antigens, respectively, appear to be more prevalent in some human carcinomas than in surrounding tissues. Tn/T antigens may represent incomplete synthesis of O-linked oligosaccharides, due to decreased activity of specific glycosyltransferases, or alternatively, increased glycosidases activity in tumors which may expose these internal O-linked oligosaccharide sequences. To explore these possibilities, we measured UDP-Gal:GalNAc alpha-R beta 1-3 galactosyltransferase (beta 3Gal-T) and Gal beta 1-3GalNAc alpha-R beta 1-3 galactosidase in a series of human breast tumors. In addition, glycoproteins extracted from the tumors were separated by SDS-PAGE and stained with the lectins HPA (GalNAc alpha-R reactive) and PNA (Gal beta-3GalNAc alpha-R reactive). The relative levels of HPA- to PNA-reactive glycoproteins in the carcinomas correlated inversely with beta 3Gal-T activities. The results suggest that Tn antigen expression in human breast carcinoma is due in part to low beta 3Gal-T activity, a situation similar to that observed previously in haematopoietic cells of individuals with a condition called Tn syndrome.
丝氨酸/苏氨酸 O 连接碳水化合物 GalNAcα 和 Galβ1-3GalNAcα,分别称为 Tn 和 T 抗原,在某些人类癌组织中似乎比周围组织中更为普遍。Tn/T 抗原可能代表 O 连接寡糖的合成不完全,这是由于特定糖基转移酶活性降低,或者是由于肿瘤中糖苷酶活性增加,从而可能暴露这些内部 O 连接寡糖序列。为了探究这些可能性,我们在一系列人类乳腺肿瘤中测量了 UDP-半乳糖:GalNAcα-Rβ1-3 半乳糖基转移酶(β3Gal-T)和 Galβ1-3GalNAcα-Rβ1-3 半乳糖苷酶。此外,从肿瘤中提取的糖蛋白通过 SDS-PAGE 分离,并用凝集素 HPA(GalNAcα-R 反应性)和 PNA(Galβ-3GalNAcα-R 反应性)进行染色。癌组织中 HPA 反应性糖蛋白与 PNA 反应性糖蛋白的相对水平与 β3Gal-T 活性呈负相关。结果表明,人类乳腺癌中 Tn 抗原的表达部分归因于 β3Gal-T 活性低,这种情况与先前在患有 Tn 综合征个体的造血细胞中观察到的情况相似。