LMP1 antagonizes WNT/β-catenin signalling through inhibition of WTX and promotes nasopharyngeal dysplasia but not tumourigenesis in LMP1(B95-8) transgenic mice

Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) can induce cell transformation and tumourigenesis, but the mechanism is not understood. Previous studies have suggested that LMP1 acts through up-regulation of cellular proliferation pathways including the Wnt/β-catenin pathway, in which β-catenin is the central effector. Increased levels of β-catenin coupled with a decrease in E-cadherin lead to reduced cell adhesion. This pathway is antagonized by WTX (Wilms' tumour gene on the X chromosome), which can promote the ubiquitination and degradation of β-catenin. In the present study, we established L2/LMP1B(95 - 8) /EGFP transgenic mice to investigate the in vivo role of LMP1. Down-regulation of WTX and E-cadherin was accompanied by increased expression of β-catenin in these mice. Even though invasive tumours did not develop, dysplasia was seen in the nasopharynx and oropharynx epithelium of these transgenic mice. Analysis of LMP1(+) , WTX(+) , and LMP1 siRNA silenced HNE-1 cell lines demonstrated that WTX could exert a dominant role in LMP1-mediated WNT/β-catenin pathway regulation. This study indicates that LMP1 antagonizes the WNT/β-catenin pathway by inhibiting WTX, and this reduction in WTX is associated with epithelial dysplasia via regulation of the WNT/β-catenin pathway molecules E-cadherin and β-catenin. Further studies are required for a better understanding of the relationship between LMP1-mediated antagonization of the WNT/β-catenin pathway and tumourigenesis.     

The expressions of claudin‐1 and E‐cadherin in junctional epithelium

Fujita T, Hayashida K, Shiba H, Kishimoto A, Matsuda S, Takeda K, Kawaguchi H, Kurihara H. The expressions of claudin‐1 and E‐cadherin in junctional epithelium. J Periodont Res 2010; 45: 579–582. © 2010 John Wiley & Sons A/S Background and Objective: The epithelium provides an important barrier against microbial invasion. Tight junction structural proteins called claudins are known to contribute to the epithelial cell barrier. Junctional epithelium is located at a strategically important interface between gingival sulcus and is interconnected by desmosomes and gap junctions, but not by tight junctions. Although claudins are tight junction‐associated proteins, they are also expressed in the epithelium despite its lack of tight junctions in invertebrates. Therefore, claudins may play an important role in junctional epithelium without tight junctions. E‐cadherin is a key molecule in the formation of adherence junctions and desmosomes. In the present study, we aimed to investigate the expressions of claudin‐1,claudin‐3, claudin‐7 and E‐cadherin in the junctional epithelium of Fischer 344 rats. Material and Methods: Gingival tissues from Fischer 344 rats were analyzed by immunohistochemical staining for claudin‐1, claudin‐3, claudin‐7, and E‐cadherin. Results: Intense staining for claudin‐1 and E‐cadherin were observed in the junctional epithelium. In contrast to claudin‐1, claudin‐3 was mainly expressed in oral gingival epithelium and claudin‐7 could not be detected on immunohistochemical analysis of the rat gingiva. Conclusion: These data suggest that claudin‐1 and E‐cadherin exist in the junctional epithelium and may play an important role in epithelial barrier function.     

胃癌血清E-钙黏附素表达及临床意义

目的:探讨胃癌患者血清中可溶性E-钙黏附素(sE-Cd)的水平与胃癌侵袭性及复发的关系。方法:用酶联免疫吸附试验(ELISA)测定20名正常人、20例胃癌术后复发患者以及80例胃癌患者术前和术后7、14d的sE-Cd水平,发现其规律,分析sE-Cd水平与胃癌的病理、临床的关系,同时检测血清癌胚抗原(CEA)和糖类抗原19-9(CA19-9)。结果:胃癌及术后复发的患者血清中sE-Cd比正常对照组明显增高,差异有统计学意义(P<0.001);术前、术后血清中sE-Cd浓度比较差异有统计学意义(P<0.001),术后血清sE-Cd浓度下降,与CEA、CA19-9较为一致。结论:sE-Cd在胃癌患者术后和复发患者血清有较高的表达,其浓度对诊断、判定手术预后和及时发现肿瘤的复发等有一定指导意义。     

E-cadherin abnormalities resulting from CPG methylation promoter in metastatic and nonmetastatic oral cancer

BACKGROUND: This study aims to compare the alterations in the methylation profiles of E-cadherin in oral cancer, especially in tumors with lowest metatastic potential. METHODS: Nine oral verrucous carcinomas (VCs), 20 oral well-differentiated squamous cell carcinomas without lymph node involvement (SCC-pN0), and 17 with lymph node involvement (SCC-pN+) were analyzed using methylation-specific polymerase chain reaction and immunohistochemical expression of E-cadherin gene. RESULTS: The immunohistochemical expression of E-cadherin in VC was significantly higher (p = .016) when compared with SCC-pN0 and SCC-pN+ groups. The E-cadherin gene methylation was not correlated with its abnormal immunohistochemical expression in VC and SCC-pN0. All tumors of the SCC-pN+ group with unmethylated E-cadherin gene showed significant loss of E-cadherin immunoexpression (p = .044). CONCLUSIONS: The E-cadherin gene methylation presence in tumors with lowest invasive and metastatic potential, such as VC, suggests the early involvement of this epigenetic event in the multistep progression of the oral carcinogenesis.     

Overexpression of E-cadherin and beta-catenin proteins in metastatic prostate cancer cells in bone

BACKGROUND: The expression of E-cadherin in the intercellular adhesion of metastatic prostate cancer cells in bone, which is the most prevalent site of metastatic growth, remains elusive. METHODS: The aim of the study was to compare the concurrent membranous expression of E-cadherin and beta-catenin proteins, the state which is known to be associated with the cellular adhesion function of E-cadherin, in prostate biopsy tissue specimens by immunohistochemical staining method. The expression patterns of E-cadherin or beta-catenin were classified as homogeneous (most cells exhibiting positively), heterogeneous (a few scattered patches of cells with positivity) or negative. RESULTS: Benign prostate hyperplasia cells exhibited homogeneous expression of both E-cadherin and beta-catenin in 9 of 11 (82%), whereas the primary prostate cancer cells were homogeneously positive for both proteins only in 4 of 22 (18%) of the cases. The results are similar to those reported in literature. However, in contrast to the primary cancer, a significantly increased frequency of the metastatic prostate cancer cells in bone exhibited homogeneous expression of E-cadherin and beta-catenin in 12 of 17 (71%) of the cases. A statistically significant association was observed between the overexpression of both proteins and the metastatic prostate cancer cells in bone (Fisher's exact P < 0.001). CONCLUSIONS: The result of the study demonstrated for the first time that the membranous overexpression of E-cadherin and beta-catenin are significantly associated with the metastatic prostate cancer cells in bone and that the high frequency of expression suggest their involvement in the intercellular adhesion of the metastatic cells in bone.