Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia
Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia
复制标题
DOI：
10.1016/j.ygyno.2005.03.043
复制
发表时间：
2005-07-01
影响因子：
4.7
通讯作者：
Kikkawa, F
中科院分区：
文献类型：
--
作者：
Shibata, K;Kajiyama, H;Kikkawa, F
Objective.葡萄糖消耗增加是恶性细胞的特征。葡萄糖通过易化葡萄糖转运蛋白转运到细胞中，已知其是超基因家族的成员。胰岛素响应性GLUT 4亚型几乎仅在胰岛素靶组织中表达。β-氨基肽酶是一种细胞表面氨肽酶，是催产素酶的同义词。β-内酰胺酶也称为与含GLUT 4的囊泡相关的胰岛素调节膜氨肽酶（IRAP）。作者评估了P-gp和GLUT 4在良性、交界性和恶性卵巢上皮中的表达。使用每种多克隆抗体对来自11例良性浆液性或粘液性囊腺瘤患者、14例浆液性或粘液性交界性肿瘤患者和80例上皮-卵巢腺癌患者（29例浆液性、17例类浆液性、14例粘液性和20例透明细胞腺癌）的福尔马林固定、石蜡包埋标本的组织切片进行P-gp和GLUT 4染色。Western blot检测卵巢癌细胞中P-Glu和GLUT-4的表达。2例良性囊腺瘤中P-β 1免疫反应阳性。II良性卵巢肿瘤均未显示GLUT 4的任何免疫反应性。14例交界性肿瘤中有7例显示P-gp免疫反应性，而14例交界性肿瘤中有5例显示GLUT 4免疫反应性。29例浆液性腺癌中23例表达P-gp，17例浆液性腺癌中15例表达P-gp，14例粘液性腺癌中13例表达P-gp，所有透明细胞腺癌均表达P-gp。在浆液性腺癌中观察到P-gp表达随分级的进展而增加的趋势。GLUT 4在29例浆液性、17例类浆液性、14例粘液性和20例透明细胞腺癌中分别有13例、13例和18例表达。浸润性癌中P-γ免疫反应性与GLUT 4免疫反应性呈正相关（r = 0.58，P < 0.01）。SKOV 3细胞中P-gp过表达可诱导GLUT 4的表达。P-gp和GLUT 4不仅可用于评估卵巢上皮恶性肿瘤，而且可作为分子治疗的靶点。P-gp和GLUT 4在卵巢癌中的作用有待进一步研究。(c)2005年爱思唯尔公司All rights reserved.
Objective. Increased glucose consumption is a characteristic of malignant cells. Glucose is transported into the cell via facilitative glucose transporters, which are known to be members of a supergene family. The insulin-responsive GLUT4 isoform is expressed almost exclusively in insulin target tissues. P-LAP is a cell surface aminopeptidase, and is a synonym for oxytocinase. P-LAP is also referred to as insulin-regulated membrane aminopeptidase (IRAP) associated with GLUT4-containing vesicle. The authors evaluated P-LAP and GLUT4 expression in benign, borderline, and malignant ovarian epithelia.Methods. Histologic sections of formalin-fixed, paraffin-embedded specimens from I I patients with benign serous or mucinous cystadenomas, 14 patients with serous or mucinous borderline tumors, and 80 patients with epithelial-ovarian adenocarcinomas (29 serous, 17 endometrioid, 14 mucinous, and 20 clear cell adenocarcinomas) were stained for P-LAP and GLUT4 using each polyclonal antibody. Expressions of P-LAP and GLUT-4 in ovarian cancer cells were detected by Western blotting.Results. P-LAP immunoreactivity was detected in 2 of I I benign cystadenomas. None of the I I benign ovarian tumors showed any immunoreactivity for GLUT4. Seven of 14 borderline tumors demonstrated P-LAP immunoreactivity, while 5 of 14 borderline tumors demonstrated GLUT4 inummoreactivity. P-LAP was expressed in 23 of 29 in serous, 15 of 17 endometrioid, 13 of 14 mucinous, and all clear-cell adeno carcinomas. The tendency toward increased P-LAP expression with advancing grade was observed in serous adenocarcinomas. GLUT4 was expressed in 13 of 29 serous, 13 of 17 endometrioid, 13 of 14 mucinous, and 18 of 20 clear-cell adenocarcinomas. In invasive carcinomas, there was a direct correlation between P-LAP inummoreactivity and GLUT4 immunoreactivity (correlation coefficient [r] = 0.58; P < 0.01). Furthermore, P-LAP overexpression in SKOV3 cells induced the GLUT4 expression.Conclusions. P-LAP and GLUT4 are available not only for the evaluation of ovarian epithelia] malignancy, but also as targets for molecular therapy. Further study to investigate the roles of P-LAP and GLUT4 in ovarian carcinoma is needed. (c) 2005 Elsevier Inc. All rights reserved.