Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Mod Pathol. 2011 Apr;24(4):533-41. doi: 10.1038/modpathol.2010.218. Epub 2010 Nov 19.
Claudin-4, encoding a protein for tight junction formation and function, is highly overexpressed in pancreatic ductal adenocarcinoma and is also associated with invasive adenocarcinomas arising in intraductal papillary mucinous neoplasms of the pancreas. However, the expression pattern of claudin-4 during neoplastic progression of intraductal papillary mucinous neoplasms remains unknown. Using quantitative real-time reverse transcription-PCR, we analyzed claudin-4 mRNA in a panel of 14 pancreatic cancer cell lines and in formalin-fixed paraffin-embedded tissues from 80 patients with intraductal papillary mucinous neoplasms of different histological grades and papillary subtypes. Increased expression of claudin-4 was confirmed in all the pancreatic cancer cell lines tested as compared with normal ductal epithelial cells and fibroblast cultures. The claudin-4 expression was significantly higher in high-grade intraductal papillary mucinous neoplasms (borderline neoplasm and carcinoma) than in low-grade intraductal papillary mucinous neoplasms (adenoma) (P<0.0001). In addition, claudin-4 mRNA levels were significantly higher in intestinal-type intraductal papillary mucinous neoplasms than in non-intestinal-type intraductal papillary mucinous neoplasms based on papillary subclassification (P<0.0001). Our findings suggest that claudin-4 expression is associated with neoplastic progression of intraductal papillary mucinous neoplasms and, especially, with a distinct pathway to intestinal differentiation.
紧密连接形成和功能的蛋白 Claudin-4 在胰腺导管腺癌中高度过表达，并且与胰腺内导管乳头状黏液性肿瘤中发生的侵袭性腺癌也有关。然而，Claudin-4 在胰腺内导管乳头状黏液性肿瘤的肿瘤进展过程中的表达模式尚不清楚。使用定量实时逆转录-PCR，我们分析了 14 种胰腺癌细胞系和 80 例胰腺内导管乳头状黏液性肿瘤患者的福尔马林固定石蜡包埋组织中 Claudin-4 mRNA 的表达。与正常导管上皮细胞和成纤维细胞培养物相比，所有测试的胰腺癌细胞系均证实 Claudin-4 表达增加。高级别胰腺内导管乳头状黏液性肿瘤（交界性肿瘤和癌）的 Claudin-4 表达明显高于低级别胰腺内导管乳头状黏液性肿瘤（腺瘤）（P<0.0001）。此外，根据乳头状分类，肠型胰腺内导管乳头状黏液性肿瘤的 Claudin-4 mRNA 水平明显高于非肠型胰腺内导管乳头状黏液性肿瘤（P<0.0001）。我们的研究结果表明，Claudin-4 的表达与胰腺内导管乳头状黏液性肿瘤的肿瘤进展有关，尤其是与特定的肠分化途径有关。
