Andrianifahanana M, Moniaux N, Schmied B M, Ringel J, Friess H, Hollingsworth M A, Büchler M W, Aubert J P, Batra S K
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, 984525 Nebraska Medical Center, Omaha, NE 68198-4525, USA.
Clin Cancer Res. 2001 Dec;7(12):4033-40.
Mucins are important biomolecules that frequently display an altered expression under pathological conditions. In a search for a unique and reliable marker(s) specific for pancreatic adenocarcinoma, we investigated the expression of different MUC genes in pancreatic tumors and tumor cell lines, in chronic pancreatitis, and in the normal pancreas.
Total RNA from 16 pancreatic tumors, 10 chronic pancreatitis tissues, 7 normal pancreas tissues, and 15 pancreatic tumor cell lines were analyzed by reverse transcription-PCR with primers specific for MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, MUC6, and MUC7 genes and by RNA slot blot analyses.
Our results revealed that of all of the mucins examined, only MUC4 displayed a differential expression that was specific for pancreatic adenocarcinoma. Indeed, a substantial number of tumor tissue samples (12 of 16) and tumor cell lines (11 of 15) expressed MUC4 mRNA, whereas samples from chronic pancreatitis (0 of 10) and the normal pancreas (0 of 7) tissues failed to exhibit any detectable level of this mucin. In contrast, no significant alteration was observed in the expression of the other mucins relative to that in the normal pancreas samples.
Overall, this work demonstrates that pancreatic mucin MUC4 is a tumor-associated mucin. Furthermore, the present study introduces a novel avenue to discriminate between pancreatic adenocarcinoma and pancreatitis. Future investigations of the role played by MUC4 in pancreatic adenocarcinoma may prove to be useful in the formulation of strategies for the diagnosis and therapeutic treatment of this malignancy.
黏蛋白是重要的生物分子,在病理条件下其表达常发生改变。为寻找胰腺腺癌特有的、可靠的标志物,我们研究了不同MUC基因在胰腺肿瘤、肿瘤细胞系、慢性胰腺炎及正常胰腺中的表达情况。
采用逆转录聚合酶链反应(RT-PCR),使用针对MUC1、MUC2、MUC3、MUC4、MUC5AC、MUC5B、MUC6和MUC7基因的特异性引物,以及RNA斑点杂交分析,对16个胰腺肿瘤、10个慢性胰腺炎组织、7个正常胰腺组织和15个胰腺肿瘤细胞系的总RNA进行分析。
我们的结果显示,在所有检测的黏蛋白中,只有MUC4表现出对胰腺腺癌具有特异性的差异表达。实际上,大量肿瘤组织样本(16个中有12个)和肿瘤细胞系(15个中有11个)表达MUC4 mRNA,而慢性胰腺炎样本(10个中有0个)和正常胰腺组织样本(7个中有0个)未检测到该黏蛋白的任何可检测水平。相比之下,与正常胰腺样本相比,其他黏蛋白的表达未观察到明显变化。
总体而言,这项工作表明胰腺黏蛋白MUC4是一种肿瘤相关黏蛋白。此外,本研究引入了一种区分胰腺腺癌和胰腺炎的新途径。未来对MUC4在胰腺腺癌中作用的研究可能有助于制定该恶性肿瘤的诊断和治疗策略。