• Childhood Kidney Diseases
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• v.17 no.2
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• pp.79-85
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• 2013

Purpose: To test whether the expression of P-cadherin, a component of slit diaphragms between podocyte foot processes, would be altered by puromycin aminonucleoside (PAN) in a cultured podocyte in vitro. Methods: Rat glomerular epithelial cells (GEpC) were cultured with various concentrations of PAN. The distribution of P-cadherin was examined with a confocal microscope. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to measure the change in P-cadherin expression. Results: This study found that P-cadherin was concentrated in the inner and peripheral cytoplasm with high concentrations of PAN under immunofluorescence views. Western blotting of GEpC revealed that PAN induced a decrease of P-cadherin in dose- and time-dependent manners. A high dose ($50{\mu}g/mL$) of PAN decreased P-cadherin expression by 21.9% at 24 h (P <0.05) and 31.9% at 48 h (P <0.01) compared to those without PAN. In RT-PCR, high concentrations ($50{\mu}g/mL$) of PAN also decreased P-cadherin mRNA expression, similar to protein suppression, by 23.5% at 48 h (P <0.05). Conclusion: Podocytes exposed to PAN in vitro concentrated P-cadherin internally, and reduced P-cadherin mRNA and protein expression. This could explain the development of proteinuria in experimental PAN-induced nephropathy.

• Childhood Kidney Diseases
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• v.9 no.2
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• pp.119-127
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• 2005

Purpose : Podocytes are critical in maintaining the filtration barrier of the glomerulus and are dependent on the integrity of slit diaphragm(SD) proteins including nephrin, p-cadherin, and others. Diabetic proteinuric condition demonstrates defects in SD molecules as well as ultrastructural changes in podocytes. We examined the molecular basis for this alteration of SD molecules especially on P-cadherin as a candidate regulating the modulation of pathogenic changes in the barrier to protein filtration. Methods : To investigate whether high glucose and AGE induce changes in SD, we cultured rat GEpC under normal(5 mM) or high glucose(30 mM) and AGE- or BSA-added conditions and measured the change of P-cadherin expression by Western blotting and RT-PCR. Results : We found that administration of high glucose decreased the P-cadherin production significantly in the presence or absence of AGE by Western blotting. In RT-PCR high glucose with or without AGE also significantly decreased the expression of P-cadherin mRNA compared to those of controls. Such changes were not seen in the osmotic control. Conclusion : We suggest that high glucose with or without AGE suppresses the Production of P-cadherin at the transcriptional level and that these changes nay explain the functional changes of SD in diabetic conditions. (J Korean Soc Pediatr Nephrol 2005;9:119-127)

• Journal of the Korea Academia-Industrial cooperation Society
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• v.11 no.3
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• pp.1133-1138
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• 2010

The purpose of our study was to evaluate the correlation between expression of VEGF, HIF-$1{\alpha}$, E-cadherin, and p53 and pathologic stage. We retrospectively reviewed the medical records of the 101 patients who underwent surgery of thyroid nodules from 2000 to 2007. Expression of VEGF, HIF-$1{\alpha}$, E-cadherin, and p53 were examinated immunohistochemically. Papillary thyroid carcinoma in this study included 54 cases of more than 45 years old. Each expression of VEGF, HIF-$1{\alpha}$, E-cadherin, and p53 was analysed. Only expression loss of E-cadherin was associated with the stage. High HIF-1 expression was significantly associated with VEGF immunoreactivity (p<0.05). Expression loss of E-cadherin was independent unfavorable factors. It is suggested that high HIF-$1{\alpha}$ expression may be associated with intratumoral neovascularization possibly through HIF-VEGF pathway.

• Journal of Life Science
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• v.19 no.6
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• pp.705-710
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• 2009

Sodium butyrate (NaBt), a naturally occurring short chain fatty acid derived from carbohydrate metabolism in the gut, is known to exhibit strong anti-cancer potentials in various human cancer cells; however, its action mechanism is poorly understood. In the present study, we demonstrated that NaBt up-regulates levels of E-cadherin, a key cell adhesion molecule implicated as a tumor suppressor, in a cell type-specific manner. Although levels of p21, a potential activator for E-cadherin expression, were also up-regulated by treatment with NaBt in several types of cells, it does not seem to be associated with the activation of E-cadherin in the NaBt-treated cells. Instead, the data from promoter analysis suggest that NaBt up-regulates expression of E-cadherin at the transcription level by enhancing its promoter strength via a CCAAT-box. The elevated E-cadherin in the presence of NaBt was primarily localized at the cell-cell contacts, converting Hep3B cells into a more differentiated form.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.6
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• pp.453-459
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• 2010

Introduction: Ameloblastic carcinoma is a rare malignant lesion, and may arise from either carcinoma ex-ameloblastoma or de novo carcinoma. Aberrant promoter hypermethylation of the tumor-associated genes leading to their inactivation is a common event in many cancer types. The p16/CDKN2/INK4A gene and p16 5 protein are involved directly in regulating the cell cycles. Cadherins are cell adhesion molecules that modulate the epithelial phenotype and regulate tumor invasion. The aim of this study was to evaluate the roles of p16 and E-cadherin methylation and loss of p16 and E-cadherin expression in the malignant transformation of an ameloblastoma. Materials and Methods: Eight cases of ameloblastoma, including 4 benign ameloblastomas without recurrence, 2 benign ameloblastomas with recurrence and 2 carcinoma ex-ameloblastomas, were examined. The promoter hypermethylation profile of the p16 and E-cadherin genes was studied using methylation-specific polymerase chain reaction (MSP) and immunohistochemical staining for p16 and E-cadherin expression. Results: 1) Aberrant CpG island methylation of the p16 gene was detected in 3 of the 4 benign ameloblastomas without recurrence and 1 of the 2 benign ameloblastomas with recurrence. 2) Aberrant CpG island methylation of the E-cadherin gene was found in 1 of the 4 benign ameloblastomas without recurrence. 3) A loss of p16 expression was noted in 1 of 4 benign ameloblastomas without recurrence and 1 of 2 carcinoma ex-ameloblastomas. 4) A loss of E-cadherin expression was noted in 2 of the 4 benign ameloblastomas without recurrence, 1 of the 2 benign ameloblastomas with recurrence and 2 of the 2 carcinoma ex-ameloblastomas. 5) A loss of p16 expression was observed in 1 of the 4 cases showing aberrant methylation of the p16 gene. 6) A loss of E-cadherin expression was observed in 3 benign ameloblastoma case showing aberrant methylation of the E-cadherin gene. Conclusion: These results suggest that loss of E-cadherin expression related to the other genetic pathway (not methylation) might be an adjuvant indicator predicting the malignant transformation of an ameloblastoma. However, the number of samples in this study was too small and the relationship between the treatment methods and clinical course were not defined. Therefore, further study will be needed.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.20
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• pp.8847-8853
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• 2014

The aim of this study was to establish the expression and localization of E-cadherin and ${\beta}$-catenin in oral squamous cell carcinomas (OSCC) so that we could correlate the findings with prognostic-relevant histopathological variables. E-cadherin and ${\beta}$-catenin expression in normal oral epithelia and in oral squamous cell carcinomas was examined immunohistochemically, and associations with histopathological differentiation and prognosis were then analyzed in 33 patients who had been operated on for OSCC. E-cadherin expression was found in (82%) of the squamous cells of well differentiated OSCC, (61%) of moderately differentiated and (39%) of poorly differentiated. E-cadherin expression was significantly associated with histological grade (p=0.000). No nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in the cytoplasm, with no correlation to the histological grade (p=0.106). ${\beta}$-Catenin expression was found in 87% of the squamous cells of well differentiated OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the expression was significantly associated with histological grade (p=0.000). the nuclear ${\beta}$-Catenin expression appeared in 3.3% of the cells and it was correlated to the histological grade (p=0.000). In (23.5%) of the cells ${\beta}$-Catenin localized in the cytoplasm, with correlation to the histological grade (p=0.002). According to this study the expression of ${\beta}$-catenin and E-cadherin were independent prognostic factors for histological grade. E-cadherin was closely linked to ${\beta}$-catenin expression in OSCC (p=0.000) and to tumor differentiation. That reflects a structural association and the role of both in tumor progression.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.12
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• pp.6455-6461
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• 2012

Objective: E-cadherin has been identified as a tumor suppressor in many types of carcinoma. However, some studies recently suggested that the role and expression of E-cadherin might be more complex and diverse. In the present study, we evaluated the prognostic value of E-cadherin expression with reference to levels in membranes and cytoplasm, and the membrane/cytoplasm ratio, in hepatocellular carcinomas (HCCs) after curative hepatectomy. Methods: The expression of E-cadherin was assessed by immunohistochemistry in HCC tissue microarrays from 125 patients, and its prognostic values and other clinicopathlogical data were retrospectively analyzed. Patients were followed for a median period of 43.7 months (range 1 to 126 months). Results: Univariate analysis demonstrated that a high membrane/cytoplasm (M/C) ratio of E-cadherin expression was associated with poor overall survival (OS) (P =0.001) and shorter time to recurrence (TTR) (P=0.038), as well as tumor size, intrahepatic metastasis, and TNM stage. In contrast, neither membrane nor cytoplasmic expression of E-cadherin was related with OS and TTR. Furthermore, multivariate analysis confirmed the M/C ratio to be an independent predictor of OS (P=0.031). ${\chi}^2$ tests additionally showed that the M/C ratio of E-cadherin expression was related with early stage recurrence (P=0.012), rather than later stage recurrence. Conclusion: The M/C ratio of E-cadherin expression is a strong predictor of postoperative survival and is associated with early stage recurrence in patients with HCC.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.1
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• pp.1-6
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• 2005

It becomes more concerned that the cell adhesion molecule plays an important role in the process of malignant transformation and tumor behaviors including invasive growth and metastasis. It is postulated if the expression of adhesion molecule is reduced in tumor tissue, the tumor cell will be undifferentiated and lose their cell adhesion ability and polarity. So the tumor cells lost the adhesion of cell to cell and to basement membrane that they became more aggressive. Reduced cadherin expression enhances invasiveness through infiltrative growth and metastasis of tumor cells is well known and mostly accepted in many epithelia tumors. We explored the expression of E-cadherin by immunohistochemical staining in 50 oral squamous cell carcinomas and investigated the correlation between the expression of E-cadherin and clinicopathologic parameters and prognosis. The expression of E-cadherin was reduced in 40/50(80%) of primary tumors, and 21/22(95.5%) of lymph nodes. The reduced expression of the E-cadherin was associated with lymph node metastasis(P=0.029), invasive mode(P=0.030) and marginal status(P=0.038). Survival analysis showed that predictive period of E-cadherin reduced group(37 months) was lower than that of E-cadherin preserved group(60 months), but there was no statistical significant difference.

• Journal of Gastric Cancer
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• v.4 no.3
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• pp.156-163
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• 2004

Purpose: While E-cadherin in normal cells induces calciumdependent cell-cell adhesion, in malignant cell, it plays a role in invasion and metastasis with a reduction of adhesion. Serum soluble E-cadherin is a result of the reduction of the cellular E-cadherin molecule and is found in the circulation of normal individuals, but it is particularly known to be increased in patients with malignancies. Accordingly, through checking the level of serum soluble E-cadherin in patients with gastric cancer and analyzing it in the view of clinicopathology, we investigated whether serum soluble E-cadherin could be translated into a clinicopathologic esult and used as a tumor marker. Materials and Methods: The investigation targeted 88 patients who had been diagnosed as having gastric cancer by the Department of Surgery, St. Mary's Hospital, from October 1, 2002, to July 30, 2003, and who had under gone performed surgery. We measured the level of preoperative serum E-cadherin in the 88 patients by unsing ELISA. Among them, we collected gastric cancer tissues from 54 patients and executed immunohistochemistry for E-cadherin. The samples were compared with normal tissues in terms of both serum E-cadherin level and immunohistochemistry level, as well as with other clinicopathologic factors. Result: The mean serum E-cadherin level of the 88 patients was 4368.7 ng/ml and was significantly higher than the level in 12 normal control patients, 3335.5 ng/ml (P=0.016). In terms of clinicopathology, the serum level of E-cadherin was significantly correlated with increasing age (P=0.0006) and was higher in positive venous invasion patients (P=0.0005). When the E-cadherin immunohistochemical stain was compared with the serum E-cadherin level in 54 patients, no significant statistically meaningful result was obtained (P=0.2881). However, 4 patients with serum E-cadherin levels about 6000 ng/ml were classified into the lower expression group ($<80\%$ of E-cadherin immunohistochemicals stain. In the analysis for 36 patients who were early gastric cancer patients, the serum E-cadherin level in lymph-node-metastatic patients was higher than it was in the other patients (P=0.0442). Conclusion: The serum E-cadherin level in gastric cancer patients was higher than the level in normal control patients. In advanced gastric cancer patients, that the difference was increased. Also, since the E-cadherin level correlated with the serum E-cadherin level with venous invasion, it can be used as an effective tumor marker for gastric cancer. Particularly, in that the serum E-cadherin level correlated with lymph node metastasis in early gastic cancer, it can be used when a therapeutic method for early gastric cancer is selected.