Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
PLoS One. 2011;6(10):e26839. doi: 10.1371/journal.pone.0026839. Epub 2011 Oct 31.
MUC16 (CA125) belongs to a family of high-molecular weight O-glycosylated proteins known as mucins. While MUC16 is well known as a biomarker in ovarian cancer, its expression pattern in pancreatic cancer (PC), the fourth leading cause of cancer related deaths in the United States, remains unknown. The aim of our study was to analyze the expression of MUC16 during the initiation, progression and metastasis of PC for possible implication in PC diagnosis, prognosis and therapy. In this study, a microarray containing tissues from healthy and PC patients was used to investigate the differential protein expression of MUC16 in PC. MUC16 mRNA levels were also measured by RT-PCR in the normal human pancreatic, pancreatitis, and PC tissues. To investigate its expression pattern during PC metastasis, tissue samples from the primary pancreatic tumor and metastases (from the same patient) in the lymph nodes, liver, lung and omentum from Stage IV PC patients were analyzed. To determine its association in the initiation of PC, tissues from PC patients containing pre-neoplastic lesions of varying grades were stained for MUC16. Finally, MUC16 expression was analyzed in 18 human PC cell lines. MUC16 is not expressed in the normal pancreatic ducts and is strongly upregulated in PC and detected in pancreatitis tissue. It is first detected in the high-grade pre-neoplastic lesions preceding invasive adenocarcinoma, suggesting that its upregulation is a late event during the initiation of this disease. MUC16 expression appears to be stronger in metastatic lesions when compared to the primary tumor, suggesting a role in PC metastasis. We have also identified PC cell lines that express MUC16, which can be used in future studies to elucidate its functional role in PC. Altogether, our results reveal that MUC16 expression is significantly increased in PC and could play a potential role in the progression of this disease.
MUC16（CA125）属于高分子量 O-糖基化蛋白家族，称为黏蛋白。虽然 MUC16 是卵巢癌的一种标志物，但它在胰腺癌（PC）中的表达模式——美国第四大癌症相关死亡原因，仍然未知。我们的研究目的是分析 MUC16 在 PC 的发生、进展和转移过程中的表达，以探讨其在 PC 诊断、预后和治疗中的可能作用。在这项研究中，使用包含健康和 PC 患者组织的微阵列来研究 MUC16 在 PC 中的差异蛋白表达。还通过 RT-PCR 测量了正常人类胰腺、胰腺炎和 PC 组织中的 MUC16 mRNA 水平。为了研究其在 PC 转移过程中的表达模式，从 IV 期 PC 患者的原发胰腺肿瘤和转移灶（来自同一患者）、淋巴结、肝脏、肺和网膜中分析组织样本。为了确定其与 PC 发生的关联，对包含不同等级的癌前病变的 PC 患者组织进行 MUC16 染色。最后，分析了 18 个人类 PC 细胞系中的 MUC16 表达。MUC16 在正常胰腺导管中不表达，在 PC 中强烈上调，并在胰腺炎组织中检测到。它首先在侵袭性腺癌之前的高级别癌前病变中检测到，这表明其上调是该疾病发生的晚期事件。与原发肿瘤相比，转移灶中的 MUC16 表达似乎更强，提示其在 PC 转移中起作用。我们还鉴定了表达 MUC16 的 PC 细胞系，可用于未来的研究以阐明其在 PC 中的功能作用。总之，我们的结果表明 MUC16 在 PC 中表达显著增加，可能在该疾病的进展中发挥潜在作用。
