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

癌细胞上表达的糖缀合物参与了转移。我们以前曾报道过，神经内膜癌主要表达I型碳水化合物链之一Lewis^b抗原。此外，我们的临床统计学研究表明，Lewis^b表达少的子宫内膜癌5年生存率低，预后差，β 1,3-半乳糖转移酶（β 1,3- gt）参与1型链的合成，β 1,4-半乳糖转移酶（β 1,4- gt）分别参与2型链的合成。为了阐明1型链和2型链在子宫内膜癌中的生物学意义，我们将人β 1,4- gt cDNA （β 1,4- gt cDNA插入表达载体pCAGGS）转染到子宫内膜癌细胞系SNG-M中，研究了转染物与SNG-M之间的生物学功能。与载体对照细胞相比，β 1,4- gt mRNA和蛋白表达较高的5种转染物对层粘连蛋白的粘附性更强，对基质的侵袭能力更强。2型糖脂Le^X的表达量高于载体对照细胞。提示β 1,4- gt表达增加的子宫内膜癌细胞与亲本细胞系相比具有不同的生物学功能。此外，我们还开发了一种新的方法来选择性地测定β 1-3和β 1-4半乳糖转移酶。该方法随后被用于测定人类妇科癌源性细胞中这两种酶的活性。来自子宫内膜癌的5个细胞系中有4个在检测的细胞系中表达了显著高水平的β 1-3GT特异性活性，而它们的β 1-4GT活性低于子宫内膜癌来源细胞中β 1-3GT活性的20%。另一方面，在子宫颈和卵巢癌细胞系中检测到β 1-4GT比β 1-3GT具有更高的特异性活性。免疫组化染色结果表明，这些结果与细胞系中Lc_4Cer-和nlc_4cer -基碳水化合物链的表达率密切相关。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