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Expression And Significance Of Autophagy Related Gene Beclin1 And MAP1LC3 In Oral Squamous Cell Carcinoma

Posted on:2012-03-17Degree:MasterType:Thesis
Country:ChinaCandidate:X Y ZhaoFull Text:PDF
GTID:2154330332999608Subject:Oral Medicine
Abstract/Summary:PDF Full Text Request
Oral squamous carcinoma is a common disease of malignant tumor of mouth, about 90% in the malignant tumor of mouth. There is steady and unremitting development in the clinical diagnose technique, but it is not ideal effective of long-term , death rate is always high.Study found that changes of autophagic activity exist in human tumors. There maintained a high autophagic activity in tumors, such as colorectal cancer, lung cancer cells , human cervical cancer and other tumor cells, it played a protective role to survive in the harsh environment for tumor cells. Autophagy can degrade intracellular proteins and organelles to provide nutrients and energy for cell,and is conducive to tumor cells growth in low blood vessels environment . Meanwhile, autophagy may also protect tumor cells by removing the damaged cell organelles to against anti-cancer therapy (such as radiotherapy, chemotherapy),make cells escape apoptosis and continue to survive. Therefore, the relationship of autophagy and tumor,development become a research focus.Gene Beclin 1 of mammalian gene encoding, named as BECN1 which is the homolog of ATG6 was the exclusive mammalian autophagy gene so far, it was a kind of anti-oncogene and specific gene participating in autophagy who made significant function in the process of autophagic vacuole forming, it was on human chromosome 17q21.Therefore, expression level of Beclin-1 display the activity of autophagy as an important factor of accommodating autophagy partly.Lipid modified format of MAP1LC3 located at endomembrane and adventitia of autophagosome, it was easy to locate at cell envelope of pre-autophagic vacuole and autophagic vacuole moreever participated in the forming of autophagosome after combined with fluorescin to make fusion protein, so MAP1LC3 was the signature protein of mammalian autophagy now.LC3 cooperated the fabrication and modification of two ubiquitin protein which made up with Atg3,Atg5,Atg7,Atg10 and Atg12 and made important effect in the forming process of mammalian autophagic vacuole, its content was direct proportion with the amount of autophagic vacuole, so expression magnitude was concerned with the activity of autophagy.Many studies indicated that Beclin-1 was concerned with Bcl-2 family of apoptosis control gene, we could strengthen apoptosis of man gastric cancer cell inducted by chemotherapeutics CDD through enhancing the activity of Caspase-9, these prompted that Beclin-1 might participate in two kinds process of programmed cell death at the same time, Beclin-1 could promote the occurrence of two kinds process of programmed cell death as the new target of gene therapy and provide new idea of oncogene therapy, it was a new target of approaching tumorigenesis, restraining tumorous growth and transfusion, studying drug tolerance of chemotherapeutics.Accordingly, this study aimed to detect the expression and clinical significance of autophagy-related genes Beclin1 and MAP1LC3 in oral squamous cell carcinoma and adjacent tissues and clinical significance with immunohistochemical method,and studied the function of Autophagy in the cell of OSCC and effection of carcinogenesis and development in squamous cell carcinoma.Test objects were 47 samples of oral squamous cell carcinoma , 16 samples of contrast group tissue of peficancerous tissues were from 1.5cm distance from the tissue of OSCC, all cases didn't do chemotherapy and radiotherapy. 30 cases were male and 17 were femal in all sample which 8 cases occurred in mouth floor, 20 cases in tongue, 6 cases in gum, 13 cases in labial part. Pathologic grading of cancer: 26 of well-differentiated cases, 21 of moderately and poorly differentiated case. 11 cases were transfuse to lymph node and 36 cases were not. immunohistochemical staining method was PV method, expression results was evaluated by the semiquantitative method of staining color and spread and did statistics analysis eventually.PV staining method discovered that masculine expression of Beclin1 and MAP1LC3 displayed as yellow or buffy grains showed in cell membrane or intracytoplasm, and squamous cell carcinoma and peficancerous tissues were all expressed at Beclin1and MAP1LC3 of autophagy related gene but amount was distinct .(1) The expression of Beclinl in squamous cell carcinoma was 31.91%(15/47), but peficancerous tissues was 75%(12/16). And the expression of MAP1LC3 in squamous cell carcinoma and peficancerous tissues was 21.28%(10/47) and 62.5﹪(10?16) respectively. teams have the difference of statistics (p﹤0.05). (2) Beclin1and MAP1LC3 in the tissue of OSCC expressed masculine and the rate lowed when malignant degree of OSCC heightened. The expression of Beclinl in well differentiated squamous cell carcinoma is 34.62%(9/26) and in medium-low differentiated is 28.57%(6/21); The expression rate of MAP1LC3 in well differentiated squamous cell carcinoma is 23.08%(6/26) and in medium-low differentiated is 19.05%(4/21), and there was no statistical significance(p>0.05).(3) The expression of Beclinl in human oral squamous cell carcinoma with lymph node metastasis and in that without is 9.09%(1/11) and 50%(18/36) respectively, the expression of MAP1LC3 in human oral squamous cell carcinoma with lymph node metastasis and in that without is respectively 0%(0/11) and 38.89%(14/36), two groups have significant difference(p﹤0.05).(4) The expression of Beclinl at tissues of mouth floor, tongue, gum and labial part was 37.5%(3/8), 45%(9/20), 33.33%(2/6)and 38.46%(5/13) respectively; The expression of MAP1LC3 at tissues of mouth floor, tongue, gum and labial part was 25%(2/8), 30%(6/20), 33.33%(2/6)and 30.77%(4/13) respectively. two groups have not significant difference(p>0.05).According to the observation of the results above all,we can conclude that:Ⅰ. Autophagy-related genes are down-regulated in OSCC, this may be related to the occurrence and development of OSCC.Ⅱ. In OSCC with lymph node metastasis, the expression of autophagy-related genes is obviously low than that without lymph node metastasis, which tells us that the abnormal expression of autophagy-related genes may be related to metastasis of OSCC.
Keywords/Search Tags:Oral squamous carcinoma, Autophagy, Microtubule-associate Protein 1 Light Chain 3, Immunohistochemistr
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