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Expression of JNK/SAPK, PPARγ, and eIF4E and Its Significance in the Cancerization of Esophagus

Author: DingTao
Tutor: ZhangXiangHong;WangFengRong
School: Hebei Medical University
Course: Pathology and Pathophysiology
Keywords: JNK p-JNK PPARγ eIF4E esophagus cancerization immunhistochemistry
CLC: R735.1
Type: Master's thesis
Year: 2007
Downloads: 181
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Abstract


Objective: Esophageal carcinoma is one of common malignant tumors in our country with the high incidence area in the south Taihang mountain areas north China. The study about pathogenesis and the mechanisms of evolution of esophageal carcinoma has become a focus.Recently, the possible relationship between signal transduction pathway and development of tumor has caused the concern of biomedical researchers. The c-Jun N-terminal kinases (JNKs), also known as stress-activated MAP kinases (SAPK), are members of the superfamily of MAP kinases. The JNK/SAPK MAP kinase pathway participates in diverse vital processes, and plays an important role in cell cycle regulation, cell proliferation and transformation. Studies showed that JNKs were involved in the pathogenesis of different diseases (including diabetes, inflammation, nerve degereneration as well as tumors).Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors belonging to the steroid/thyroid/retinoid receptor superfamily of ligand-activated transcription factors. PPARs could promote the transcription of target nuclear genes. PPARs are on the cross-point of several transcriptional signaling pathways, and play very important roles in pathogenesis of metabolic diseases and cancer. The PPARs subtypes, especially PPARγ, was closely related with cancer.Eukaryotic translation initiation factor 4E (eIF4E) is a 25 kDa protein that binds to the mRNA“cap”during an early step in the initiation of protein synthesis. Studies showed that the expression of eIF4E was increased in many tumors and cell lines. The overexpression of eIF4E could change the phenotype of cells, promote cell proliferation, induce cell malignant transformation, and promote tumor formation and metastasis.JNK/SAPK, PPARγand eIF4E are all important factors involving in the proliferation and malignant transformation of cells. Works on the putative roles of JNK/SAPK, PPARγand eIF4E in the initiation, development of tumors and their clinical pathological significance in many tumor could be seen in the literatures. Yet, few studies were involved the relationship between JNK/SAPK, PPARγand eIF4E. Works on the putative roles of the expression of JNK/SAPK, PPARγand eIF4E in the carcinogenesis of esophagus have not been seen in the literature.Dysplasia of esophageal squamous epithelium is the precancerous lesion of esophageal carcinoma. Cancerous change of esophageal dysplasia is very important way of carcinogenesis of ESCC. To further explore the carcinogenesis of esophageal carcinoma, the expression of JNK, p-JNK, PPARγand eIF4E in the esophageal normal mucosa, atypical hyperplasia and squamous cell carcinoma were comparatively studied with immunohistochemical staining.Method: 1 The expression of JNK, p-JNK, PPARγand eIF4E was studied in 15 cases of normal esophageal epithelium; 70 cases of dysplasia (including 24 cases of low-grade dysplasia, 26 cases of moderate-grade dysplasia, 20 cases of high-grade dysplasia); 75 cases of esophageal squamous cell carcinoma (including 15 cases of carcinoma in situ, 20 cases of well-differentiated squamous cell carcinoma, 20 cases of moderately differentiated squamous cell carcinoma and 20 cases of poorly differentiated squamous cell carcinoma) by Power VisionTM-9000 (PV-9000) immunohistochemical staining method. The clinical pathological significances of JNK, p-JNK, PPARγand eIF4E expression were analyzed. 2 The experimental data were statistically analyzed with Chi-square test, Fisher’s exact test and correlation analysis with statistics software of SPSS13.0 edition.Results: 1 Expressions of JNK in different groups: Immunohistochemical staining results showed the positive expression rate of JNK was 20.0%, 35.7% and 54.7% respectively in normal esophageal tissue, dysplasia and ESCC. The positive expression of JNK was significantly higher in ESCC than that in normal esophageal tissue and dysplasia (P<0.05). The positive expression of JNK in ESCC was decreased significantly in the cases of poorly differentiated squamous cell carcinoma than that in well-differentiated and moderately differentiated squamous cell carcinoma (P<0.05). Further analysis showed that among the different dysplasia cases, the positive expression of JNK was significantly higher in the cases of high-grade dysplasia than that in normal esophageal tissue and low-grade and moderate-grade dysplasia (P<0.05).2 Expressions of p-JNK in different groups: The positive expression rate of p-JNK in normal esophageal tissue, esophageal dysplasia and ESCC was 33.3%, 52.9% and 70.7% respectively. From normal esophageal tissue, esophageal dysplasia to ESCC, the expression of p-JNK was increased accordingly. The positive expression of p-JNK in ESCC was significantly higher than that in normal esophageal tissue and esophageal dysplasia (P<0.05). The positive expression of p-JNK in ESCC was closely related with the degree of differentiation. The positive expression rate in the cases of poorly differentiated squamous cell carcinoma was decreased significantly than that in well-differentiated and moderately differentiated squamous cell carcinoma (P<0.05). The positive expression of p-JNK was increased significantly in the cases of high-grade dysplasia than that in normal esophageal tissue and low-grade and moderate-grade dysplasia (P<0.05).3 Expressions of PPARγin different groups: Immunohistochemical staining results showed the positive expression rate of PPARγwas 73.3%, 48.6% and 44% respectively in normal esophageal tissue, dysplasia and ESCC. The positive expression of PPARγwas decreased significantly in ESCC than that in normal esophageal tissue (P<0.05). Among the ESCC cases, the positive expression of PPARγwas decreased significantly in the cases of poorly differentiated squamous cell carcinoma than that in well-differentiated and moderately differentiated squamous cell carcinoma (P<0.05). In the different dysplasia cases, the positive expression of PPARγwas increased significantly in the cases of high-grade dysplasia than that in low-grade and moderate-grade dysplasia (P<0.05), and than that in the cases of carcinoma in situ (P<0.05).4 Expressions of eIF4E in different groups: The results showed the positive expression rate of eIF4E was 26.7%, 40% and 64% in normal esophageal tissue, dysplasia and ESCC. The positive expression of eIF4E was increased significantly in ESCC than that in normal esophageal tissue and dysplasia (P<0.05). In ESCC cases, the positive expression of eIF4E was significantly higher in the cases of poorly differentiated squamous cell carcinoma than that in well-differentiated squamous cell carcinoma (P<0.05).5 Relationship between the expression of JNK and p-JNK: Statistical analysis results showed that the positive coexpression rate of JNK and p-JNK increased from normal esophageal tissue, esophageal dysplasia to ESCC. The expression of JNK and p-JNK was in good accordance (P<0.05).6 Relationship between the expression of JNK, p-JNK, PPARγand eIF4E in ESCC: Positive correlation between JNK and p-JNK positive expression as well as JNK and PPARγpositive expression could be found between the expression of JNK and PPARγ(P<0.05), and between the expression of JNK and p-JNK (P<0.05); Positive expression of JNK and eIF4E was opposite relationship in ESCC that accompany the increasing of pathological grading, inverse correlation could be found between the expression of JNK and eIF4E (P<0.05).7 The clinical pathological significance of JNK, p-JNK, PPARγand eIF4E expression: The expression of JNK, p-JNK, PPARγand eIF4E were not related with sex, and age of patient, location, size of tumor and depth of invasion, lymph node metastasis (P>0.05).Conclusions: 1 The expression of both JNK and p-JNK in ESCC was significantly higher than that in normal esophageal squamous epithelium and esophageal dysplasia. In the cases of ESCC, the expression of JNK and p-JNK was decreased as the decrease of differentiation, suggesting that JNK and p-JNK may play an important role in the carcinogenesis and progression of the esophageal squamous carcinoma.2 The expression of PPARγin ESCC was significantly lower than in normal esophageal squamous epithelium. Among the ESCC cases, the expression of PPARγwas positively related with the differentiation. On the contrary, the expression of eIF4E in ESCC was significantly higher than in normal esophageal squamous epithelium and esophageal dysplasia, and eIF4E expression in ESCC was negatively related with the differentiation, suggesting that PPARγand eIF4E may be involved in the carcinogenesis and progression of esophageal squamous carcinoma.3 In the cases of ESCC, the expression of JNK was positively correlated with that of PPARγand negatively correlated with that of eIF4E, suggesting that JNK may involve in the regulation of PPARγand eIF4E.

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CLC: > Medicine, health > Oncology > Gastrointestinal Cancer > Esophageal tumors
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