| Esophageal cancer derives from the abnormal proliferation of esophageal squamous or glandular epithelium. The progression of esophageal cancer involves multiple factors and genes, and slowly goes through different stages (mild dysplasia, moderate dysplasia, severe dysplasia and invasive esophageal carcinoma).In the pathology, esophageal cancer can be divided into esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma. While China is one of the countries with high incidence of ESCC. Currently, with the development of molecular biology, the mechanism of ESCC have been paid a lot of attention.At the beginning of our research,10 specimens of ESCC tissue,7 specimens of precancerous tissue and 29 specimens of tissue from either incisal margin or distal normal tissues were assayed by Whole Human Genome Oligo Microarray. And we found that 333 genes were differently expressed between pathological tissues and normal tissues, from which 9 genes were screened out as candidate genes. More researches were be done on Aurora-A(Aurora kinases A), one of the 9 candidate genes. Human Aurora-A is found overexpressed in several human cancers. Aurora-A encodes an evolutionarily conserved serine/threonine protein kinase, participates in the regulation of cellular mitosis and maintains the integrity of the genome. Our lab first discovered Aurora-A had a relationship with ESCC in 2004, and have done a lot of research on Aurora-A. However, the expression and the mechanism of Aurora-A in the precancerous stage of ESCC remains unknown Firstly, we used Real-time PCR experiment to confirm the above microarray results. Aurora-A expressed higher in 6 cases of precancerous tissues and 3 cases of ESCC tissues than in normal tissues with a significant difference in the rate of 75.0%(6/8) and 60.0%(3/5), separately. Compared with immortalized esophageal epithelium cell lines, the expression of Aurora-A was significantly higher in ESCC cell lines. Secondly, tissue microarray and immunohistochemistry was employed to detect the expression patterns of Aurora-A in 9 cases of severe dysplasia and 122 cases of ESCC combined with adjacent precursor lesions. The result showed that the positive rate of Aurora-A in normal esophageal epithelium, mild dysplasia, moderate dysplasia, severe dysplasia and ESCC was 17.2%,27.6%,50.0%,77.9% and 84.3%, respectively. A progressive increase was along with the grade of the lesion (r=0.548,P<0.001).At last, we evaluated the alteration of cell growth and migration by growth curve and transwell assay in Aurora-A-transfected cells. And we found that the Aurora-A-transfected clones promoted cells growth and increased the migration when compared with vector alone. Therefore, our research showed that the expression of Aurora-A was increased in ESCC and precancerous lesions. Aurora-A could be involved in the development and progression of ESCC.And Aurora-A might provide a new way for early diagnosis and treatment of ESCC in the future.In part two, we studied the expression of Nlp (ninein like protein) in ESCC and the precancerous lesions. Nlp is a centrosomal protein which was found by our laboratory through yeast two hybird. Plenty of evidence have linked Nlp to human cancer, indicating that Nlp is involved in tumourigenesis.We investigated the expression level of Nlp in 10 cases of severe dysplasia and 133 cases of ESCC combined with adjacent precursor lesions. The result showed that the positive rate of Nlp in normal esophageal epithelium, mild dysplasia, moderate dysplasia, severe dysplasia and ESCC was 11.0%,27.8%, 50.0%,80.0% and 94.1%, respectively. A progressive increase was along with the grade of the lesions. Nlp expression was up-regulated with the increasing grade of esophageal lesion (r=0.526, P< 0.001), which indicated that Nlp could be involved in the development and progression of ESCC and esophageal dysplasia. In addition, we evaluated the alterations of cell growth and migration by growth curve and transwell assay in Nlp-transfected cells. And we found that the Nlp-transfected clones increased the migration when compared with vector alone, but did not promote cell growth. Therefore, our study clearly indicated the expression of Nlp was increased in ESCC and precancerous lesions. And the increased expression of Nlp could be involved in the development and progression of ESCC and precancerous lesions. |
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