Correlation Between P53 Protein And Akt Protein In Esophageal Cancer

PurposeEsophageal cancer is one of the most common malignant tumors in the world,accounting for 2%of all malignant tumors,and about 400 thousand people die of esophageal cancer every year.China is one of the high incidence areas of esophageal cancer.Dysregulation of the expression of oncogenes and tumor suppressor genes leads to changes in the intracellular signaling pathways,leading to the development and progression of cancer cells.P53 is an important tumor suppressor gene in human body.Akt is an important oncogene.In normal human cells,both of them are in dynamic balance,which regulate cell proliferation and apoptosis.The imbalance of apoptosis and proliferation of cancer cells showed that the expression of P53 and Akt in the cells was changed compared with the normal human cells.This paper aims to explore the relationship between two upstream signaling pathway node:P53 and Akt protein in esophageal carcinoma cells,identify its biological characteristics in cancer cells,leading to a better understanding of the occurrence and development of tumor cells.MethodThe resected esophageal carcinoma and adjacent tissues were made into pathological sections and examined by immunohistochemistry.Then detect the p-Aktl,p-Akt2,Akt and P53 protein expression in esophageal squamous cell carcinoma;Extracting TE-1 cell protein and Western blot method was used to detect the p-Akt1,p-Akt2,Akt and P53 concentration;then adding P53 inhibitor Pifithrin-alpha,Aktl inhibitor A-674563,Akt2 inhibitor CCT128930 to TE-1 cells separately,protein was extracted from TE-1 cell after treatment for detection of p-Aktl,p-Akt2 and P53 concentration;Sequencing the p53,akt1,akt2 exon gene in human esophageal cancer tissues,comparing with the GENEBANK to found that the mutation and then compared with the literatures to identify the mutation type.ResultsIn 50 cases of esophageal carcinoma,respectively 52%(26/50),42%(21/50),30%(15/50),66%(33/50)cases express P53,Akt,p-Aktl and p-Akt2 protein,the ratio were 22%(11/50),18%(9/50),8%(4/50),28%(14/50)in paracancerous tissues,significantly more P53(p=0.002),Akt(p=0.009),p-Akt1(p=0.005)and p-Akt2(p=0.000)protein were expressed in esophageal carcinoma tissures.Compared with middle and high differentiation of esophageal cancer cell group,stage ? +? group,lymph node metastasis group,P53 protein in poorly differentiated esophageal cancer group,esophageal,stage ? +? group and no lymph node metastasis group were not significantly increase(p>0.05).The expression of Akt,p-Aktl and p-Akt2 protein was also not significantly increased in poorly differentiated group and stage ?+? group(p>0.05).;Akt,p-Akt1 and p-Akt2 protein expression increased significantly in lymph node metastasis group(p<0.05).Compared with the control group,P53,Akt,p-Akt1 expression was decreased after using Pifithrin-alpha(p=0.002,p=0.032,p=0.016);the expression of p-Akt2 was not obviously decreased(p=0.133);P53,Akt,p-Akt1 expression was decreased after using A-674563(p=0.004,p=0.004,p=0.011);the expression of p-Akt2 was not obviously decreased(p=0.519).P53,Akt,p-Akt1,p-Akt2 expression was decreased after using CCT128930,the difference was statistically significant(p=0.014,p=0.013,p=0.010,p=0.005).R175H,H179R,R248Q and R273H mutations were not detected in 50 specimens of esophageal carcinoma.ConclusionMore P53,Akt,p-Akt1 and p-Akt2 protein were expressed in esophageal carcinoma than normal tissues,and Akt,p-Aktl and p-Akt2 protein may be involved in lymph node metastasis of esophageal cancer cells.Different with the suppression relationship between P53 and Akt protein in the normal tissue,P53 promote with Aktl and Akt2 protein each other in esophageal carcinoma,and the development of tumor cells is mediated.However,the change of the relationship between these proteins is not the cause of the mutation of P53R175H,H179R,R248Q and R273H in the p53 gene.Further studies are needed to elucidate the mechanism.