Alteration of endometrial cancer cell function caused by beta 1,4-galactosyl transferase gene induction.

癌细胞上表达的糖偶联物参与了转移。我们以前曾报道，内膜癌主要表达Lewis^b抗原，这是一种I型碳水化合物链。此外，我们的临床统计研究表明，Lewis^b低表达的子宫内膜癌患者的5年生存率和预后较低，β1，3-半乳糖基转移酶(β1，3-GT)参与了I型链的合成，β1，4-半乳糖基转移酶(β1，4-GT)参与了2型链的合成。为了阐明人β1，4-GT基因在子宫内膜癌中的生物学意义，我们将人β1，4-GT基因(β1，4-GT基因插入表达载体pCAGGS)导入子宫内膜癌细胞系SNG-M，并研究了其与SNG-M细胞的生物学功能。5种β1，4-GT基因和蛋白表达水平较高的细胞对层粘连蛋白和内毒素…有较强的粘附性与载体对照细胞相比，对基质的离子能力更强。转基因细胞中2型糖脂Le^X的表达高于载体对照细胞。提示子宫内膜癌细胞β1，4-GT表达增加可能具有与亲本细胞不同的生物学功能。此外，我们建立了选择性检测β1-3和β1-4半乳糖基转移酶的新方法。然后，该方法被用于测定人类妇科肿瘤来源细胞中这两种酶的活性。在5个子宫内膜癌来源的细胞系中，有4个细胞株的β1-3GT比活性显著升高，而子宫内膜癌来源细胞中的β1-4GT活性低于β1-3GT的20%。另一方面，在子宫颈癌和卵巢癌细胞系中，β1-4GT的比活性高于β1-3GT。因此，根据免疫组织化学染色的结果，这些发现与基于LC_4Cer和NLC_4Cer的碳水化合物链在细胞系中的表达密切相关。较少

Glycoconjugates expressed on cancer cells are involved in the metastases. We have previously reported that endornetrial cancer expressed predominantly Lewis^b antigen, one of the type I carbohydrate chain. Furthermore, our clinicostatiscal study has revealed that endometrial cancer with little expression of Lewis^b showed a low 5 years survival rate, prognosis, beta 1,3-galactosyltransferase (beta 1,3-GT) is involved in the synthesis of type 1 chain, and beta 1,4-galactosyltransferase (beta 1,4-GT) is involved in the synthesis of type 2 chain, respectively. In order to elucidate the biological significance of the type 1 chain and type 2 in endometrial cancer, we transfected human beta 1,4-GT cDNA (beta 1,4-GT cDNA inserted expression vector pCAGGS) into endometrial cancer cell line, SNG-M and studied the biological function between transfectants and SNG-M.Five transfectants with greater expression of beta 1,4-GT mRNA and proteins showed greater adhesiveness to laminin and greater invas … More ion abiligy to matrigel compaired to vector control cells. Expression of type 2 glycolipid Le^X of transfectant was higher than that of vector control cells. It is suggested that endometrial cancer cell with increased expression of beta 1,4-GT could have different biological function compared with parental cell line.Furthermore, we have developed a new procedure for the selective determination of beta 1-3 and beta 1-4 galactosyltransferases. The method was then used to determine the activities of both enzymes in human gynecological carcinoma-derived cells. Four of the five cell lines derived from uterine endometrial cancer expressed significantly high levels of specific activity of beta 1-3GT among the cell lines examined, while their beta 1-4GT activities were less than 20% of that for beta 1-3GT in the endometrial carcinoma-derived cells. On the other hand, a higher specific activity of beta 1-4GT than that of beta 1-3GT was detected in the cell lines derived from uterine cervical and ovarian cancers. These findings were thus found to correlated closely with the rate of expression of Lc_4Cer- and nLc_4Cer-based carbohydrate chains in the cell lines based on the results of immunohistochemical staining. Less