MECHANISMS UNDERLYING ABERRANT GLYCOSYLATION OF MUC1 MUCIN IN BREAST-CANCER CELLS
MECHANISMS UNDERLYING ABERRANT GLYCOSYLATION OF MUC1 MUCIN IN BREAST-CANCER CELLS
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DOI：
10.1111/j.1432-1033.1995.607_2.x
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发表时间：
1995-10-15
期刊：
影响因子：
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通讯作者：
TAYLORPAPADIMITRIOU, J
中科院分区：
文献类型：
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作者：
BROCKHAUSEN, I;YANG, JM;TAYLORPAPADIMITRIOU, J
MUC 1基因的产物，即多态性上皮粘蛋白（PEM）在乳腺癌和其他癌症中异常糖基化，导致通常隐藏的肽表位暴露。乳腺癌细胞表达的PEM含有更多的唾液酸化O-聚糖，并且具有比正常细胞表达的更低的GlcNAc含量。因此，肽表位的暴露被认为是由于肿瘤相关粘蛋白上的糖侧链较短。为了研究乳腺癌细胞中不同糖基化模式的潜在可能机制，我们分析了正常和癌性乳腺上皮细胞中粘蛋白O-聚糖链生物合成所涉及的途径。研究了来源于正常人乳的永生化乳腺上皮细胞系MTSV 1 -7和三种人乳腺癌细胞系BT 20、MCF-7和T47 D。在正常乳腺细胞系中存在组装、延长和终止O-聚糖核心-1 [Gal β 1-3GalNAc α-R]和核心-2 [GlcNAc β 1-6（Gal β 1-3）GalNAc α-R]的糖基转移酶活性。许多糖基转移酶的活性也在乳腺癌细胞中以不同的水平表达。然而，在所有三种癌细胞系中，唾液酸转移酶活性（CMP-唾液酸Gal β 1-3GalNAc α 3-唾液酸转移酶）增加数倍。此外，乳腺癌细胞系BT 20和T47 D已经丧失了合成核心-2的能力，如通过缺乏UDP-GlcNAc：Gal β 1-3GalNAc（GlcNAc至GalNAc）β 6-GlcNAc-转移酶活性所示，这对应于mRNA转录物的缺乏。然而，MCF-7乳腺癌细胞表达这种酶。因此，BT 20和T47 D细胞中肽表位暴露的机制被认为是核心-2分支的丢失，导致更短的唾液酸化O-聚糖链。对MCF-7乳腺癌细胞提出了不同的机制。
The product of the MUC1 gene, the polymorphic epithelial mucin (PEM) is aberrantly glycosylated in breast and other carcinomas, resulting in exposure of normally cryptic peptide epitopes. PEM expressed by breast cancer cells contains more sialylated O-glycans and has a lower GlcNAc content than that expressed by normal cells. The exposure of peptide epitopes is thus thought to be due to the sugar side chains being shorter on the tumour-associated mucin. To investigate possible mechanisms underlying the different pattern of glycosylation in breast cancer cells, we analysed the pathways involved in the biosynthesis of O-glycan chains of mucins in normal and cancerous mammary epithelial cells. An immortalized mammary epithelial cell line originating from normal human milk, MTSV1-7, and three human breast cancer cell lines, BT20, MCF-7 and T47D, were studied. Glycosyltransferase activities assembling, elongating and terminating O-glycan core-1 [Gal beta 1-3GalNAc alpha-R] and core-2 [GlcNAc beta 1-6 (Gal beta 1-3) GalNAc alpha-R] were present in the normal mammary cell line. Many of the glycosyltransferase activities were also expressed at variable levels in breast cancer cells. However, a sialyltransferase activity (CMP-sialic acid Gal beta 1-3GalNAc alpha 3-sialyltransferase) was increased several fold in all three cancer cell lines. Moreover, mammary cancer cell lines BT20 and T47D have lost the ability to synthesize core-2, as shown by the lack of UDP-GlcNAc: Gal beta 1-3GalNAc (GlcNAc to GalNAc) beta 6-GlcNAc-transferase activity, which corresponded to the absence of the mRNA transcript. However, MCF-7 breast cancer cells expressed this enzyme. Thus, the mechanism for the exposure of peptide epitopes in BT20 and T47D cells is proposed to be the loss of core-2 branching leading to shorter, sialylated O-glycan chains. A different mechanism is proposed for MCF-7 breast cancer cells.