Expression and Functions of Transmembrane Mucin MUC13 in Ovarian Cancer
Expression and Functions of Transmembrane Mucin MUC13 in Ovarian Cancer
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DOI：
10.1158/0008-5472.can-08-0587
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发表时间：
2009-02-01
期刊：
影响因子：
11.2
通讯作者：
Jaggi, Meena
中科院分区：
文献类型：
--
作者：
Chauhan, Subhash C.;Vannatta, Kelley;Jaggi, Meena
MUC 13是一种跨膜粘蛋白，通常在胃肠道和气道上皮中表达。它的异常表达与胃、结肠及肿瘤的发生有关。然而，MUC 13在卵巢癌中的表达和功能尚不清楚。本研究分析了MUC 13的表达谱和功能，以阐明其在卵巢癌诊断和发病机制中的潜在作用。使用最近产生的单克隆抗体（克隆PPZ 0020）通过免疫组织化学使用卵巢癌组织微阵列和56个另外的上皮性卵巢癌（EOC）样品来确定MUC 13的表达谱。MUC 13在卵巢癌组织中的表达显著高于正常卵巢组织和良性卵巢组织（P < 0.005）。在所有卵巢癌类型中，MUC 13表达特异性地存在于EOC中。为了进行功能分析，将克隆在pcDNA3.1中的全长MUC 13基因在MUC 13无效卵巢癌细胞系SKOV-3中表达。在这里，我们表明，外源性MUC 13表达诱导的形态学变化，包括散射的细胞。这些变化通过c-Jun NH（2）激酶（JNK）化学抑制剂（SP 600125）或JNK 2 siRNA消除。此外，在外源性MUC 13表达后，在异种移植小鼠模型系统中观察到细胞-细胞粘附的显著降低和细胞运动性、增殖和肿瘤发生的显著（P < 0.05）增加。这些细胞特征与HER 2、p21活化激酶1和p38蛋白表达的上调相关。我们的研究结果表明MUC 13在卵巢癌中的异常表达，其表达改变了SKOV-3细胞的细胞特性。这意味着MUC 13在卵巢癌中的重要作用。[Cancer Res 2009;69（3）：765-74]
MUC13, a transmembrane mucin, is normally expressed in gastrointestinal and airway epithelium. Its aberrant expression has been correlated with gastric colon and cancer. However, the expression and functions of MUC13 in ovarian cancer are unknown. In the present study, the expression profile and functions of MUC13 were analyzed to elucidate its potential role in ovarian cancer diagnosis and pathogenesis. A recently generated monoclonal antibody (clone PPZ0020) was used to determine the expression profile of MUC13 by immunohistochemistry using ovarian cancer tissue micro-arrays and 56 additional epithelial ovarian cancer (EOC) samples. The expression of MUC13 was significantly (P < 0.005) higher in cancer samples compared with the normal ovary/benign tissues. Among all ovarian cancer types, MUC13 expression was specifically present in EOC. For the functional analyses, a full-length MUC13 gene cloned in pcDNA3.1 was expressed in a MUC13 null ovarian cancer cell line, SKOV-3. Here, we show that the exogenous MUC13 expression induced morphologic changes, including scattering of cells. These changes were abrogated through c-Jun NH(2) kinase (JNK) chemical inhibitor (SP600125) or JNK2 siRNA. Additionally, a marked reduction in cell-cell adhesion and significant (P < 0.05) increases in cell motility, proliferation, and tumorigenesis in a xenograft mouse model system were observed upon exogenous MUC13 expression. These cellular characteristics were correlated with up-regulation of HER2, p21-activated kinase 1, and p38 protein expression. Our findings show the aberrant expression of MUC13 in ovarian cancer and that its expression alters the cellular characteristics of SKOV-3 cells. This implies a significant role of MUC13 in ovarian cancer. [Cancer Res 2009;69(3):765-74]