Analysis of mucin glycoproteins in the gallbladder of BK5.erbB2 transgenic mouse

胆囊癌的总体预后很差，因为手术时晚期病例的比例很高，因此治愈率较低。PT2癌局限于胆囊壁，因此可预期有较高的治愈率和较好的预后。然而，预后并不一定很好，因为在一些pt2癌病例中发现了远处复发。在癌变过程中，粘蛋白糖硅化的改变，如粘蛋白核心蛋白O-糖基化位点的改变或糖结构唾液酸化的增强，都是已知的。粘蛋白类型的O-糖硅化是由GalNAc-T同工酶启动的，腺癌细胞中的O-糖硅化是由GalNAc-T3催化的。在PT2胆囊癌中，GalNAc-T3在PT2癌中的差异表达可能通过改变O-…而影响粘蛋白的生物学特性，从而调节癌细胞的恶性行为更多的糖硅化。被单抗MY.1E12识别的唾液酸化的MUC1(Jpn J Cancer res 1996；87：488-496)已被用作侵袭性腺癌的标志物。在pt2胆囊癌中，唾液酸化的My间质定位蛋白高水平表达。1侵袭部位的E12-反应-MUC1与疾病的侵袭性有关，如形成远处转移的倾向。BK5.过度表达erbB2的ErbB2转基因小鼠发生胆囊癌的发病率较高。近年来，研究发现唾液粘蛋白复合体MUC4通过与受体的直接相互作用影响酪氨酸激酶的活性，促进哺乳动物肿瘤细胞的生长。另外，在转基因小鼠中，Muc4的上调及其与erbB2的相互作用可能通过调节受体酪氨酸激酶的磷酸化而参与胆囊癌的发生过程，因此，致癌粘蛋白糖蛋白糖链的改变增强了肿瘤的侵袭和/或转移能力，Muc4可能通过激活erbB2在胆囊癌的发生中发挥重要作用。较少

The overall prognosis of gallbladder carcinoma is poor because of a high percentage of advanced cases at the time of operation and thereby a lower curability. pT2 carcinoma is limited in the gallbladder wall, and therefore a high curability as well as a better prognosis can be expected. However, the prognosis has not been necessarily good since distant recurrences are found in some cases of pT2 carcinomas. Alterations in glycosilation of mucins, such as an alteration in the site of O-glycosylation of mucin core proteins or an enhanced sialylation of carbohydrate structures, are known in the process of malignant transformation.Mucin-type O-glycosilation is initiated by GalNAc-T isozymes and O-glycosilation in adenocarcinoma cell lines is reportedly catalyzed by GalNAc-T3. In pT2 gallbladder carcinoma, the differential expression of GalNAc-T3 in pT_2 carcinoma may modulate the malignant behavior of the carcinoma cells by affecting the biological properties of mucins due to the altered O- … More glycosilation.Sialylated MUC1 recognized by a mAb MY.1E12 (Jpn J Cancer Res 1996;87:488-496) has been used as a marker for invasive adenocarcinomas. In pT2 gallbladder carcinoma, the high level expression of stromal localization of sialylated MY. 1E12-reactive-MUC1 at the invading sites correlates with the aggressiveness of the disease, such as the tendency to form distant metastasis.BK5.ErbB2 transgenic mice overexpressing erbB2 develop gallbladder carcinoma at a high incidence. Recently, Muc4 (sialomucin complex) has been shown to influence erbB2 (tyrosine kinase) activity through direct interaction with the receptor and to potentiate tumor growth in mammalian carcinoma cells. Also in the transgenic mice, up-regulation of Muc4 and its interaction with erbB2 may be involved in the process of gallbladder carcinogenesis through modulation of phosphorylation of the receptor tyrosine kinase.Thus, alterations in carbohydrate chains of carcinoma-producing mucin glycoproteins potentiate the capability of tumor invasion and/or metastasis and Muc4 may play an important role in gallbladder carcinogenesis through the activation of erbB2. Less