The Protein Expression And Significance Of MTOR, EIF4E And 4EBPS In Breast Cancer Tissue

Breast cancer, a serious threat to women's health, is one of the most common malignant tumors that women have got. It has the highest incidence in European and American. In 2007, there are 178,480 new-added breast cancer patients, accounting for 26% of the total number of the tumour cases. The mortality rate of this cancer is in the second place, just behind bronchogenic carcinoma. Although breast cancer in Asia is slightly lower compared with Europe and America, in recent years, it also shows a clearly increasing trend. In China, in the past 20 years, the incidence of breast cancer is rising, and there seems to be an accelerating trend. In many areas, breast cancer has been in the first place of the female malignant tumors. Studies on epidemiology, genetics and animal model of chemical carcinogen, as well as molecular genetics show that the incidence of malignant tumors is a long-term, multi-factor participating in and multistage process. Studies show that in many pathogenic factors, the cell signaling abnormity keeps a close relationship with tumor. In many signaling pathways, some abnormal proteins cause tumor cell synthesize a large number of somatomedins, which finally result in the lose control of cell proliferation.Mammlalian target of rapamycin, mTOR is a protein kinase which is generated by rapamycin in mammals. Also it is an atypical serine/threonine and its protein molecular weight is 289kDa, including 2549 amino acid. mTOR signaling pathways play a very important role in regulating cell's differentiation, growth, proliferation and apoptosis. In the bodies of mammals, the main function of mTOR is to regulate the translation process. Eukaryotic translation initiation factor 4E, eIF4E is a downstream site of mTOR's signaling pathways and the most effective adjustment factor to limit speed in the process of translation of mRNA. It plays an important role of regulation in the initial stage of protein synthesis. EIF4E is one of the newly discovered proto-oncogenes. Its encoded protein is a cap binding phosphoprotein existing in cytoplasm and can be combined with eIF4G and eIF4A to form a translation initiation complex. It also can be connected with 40S subunit of eukaryotic cell ribosome to start the process of translation. Eukaryotic initiation factor 4E binding proteins (eIF4E 4E proteins,4EBPS) contain three related polypeptide families:4EBPI,4EBP2,4EBP3. Each can combine with eIF4E and restrain the combination between eIF4E and the cap. When 4EBPS become phosphorylation, it can release eIF4E and can combine with eIF4G and eIF4A to form translation initiation complex so as to improve protein's translation efficiency. When 4EBPS becomes hypophosphorylation, it can combine with eIF4E to restrain the dependence of the cap on initial translation. Therefore, mTOR signaling pathways of downstream sites and downstream substrates---eIF4E and 4EBPS, respectively play an important adjustment function for the growth of cells. The main biological characteristics of malignant tumors are abnormal growth and unlimited proliferation of cells. The abnormity of signaling pathways mediated by mTOR is closely related with the incident of many malignant tumors. However, as to mTOR, eIF4E and 4EBPS's protein expression and their relationship with the breast cancer, as well as the study on metastasis, reports have not yet been seen in literatures.This study adopts immunohistochemical SP method to detect eIF4E, mTOR and 4EBPS's protein expression in breast cancer tissue and surgical margin of normal breast tissue and to discuss the expression and the clinicopathological significance of eIF4E mTOR 4EBPS in breast cancer tissue.Materials and methods:1. SP immunohistochemical method is adopted to detect the protein expression of eIF4E, mTOR, and 4EBPS in 45 cases of breast cancer tissue,45 cases of surgical margin of normal breast tissue and corresponging lymph node.2. Statistical processing:All data has been analyzed through statistic software SPSS13.0. X2 is used to compare positive rates, while spearman related inspection and analysis are used for the detection of correlation between positive rates. When a=0.05, it is believed to be significant inspection.Results:1. The positive rate of expression of mTOR in normal breast tissue is 20.00% while it is 75.56% in breast cancer, which is significantly higher than normal tissue (P<0.05). The positive rate of expression in the lymph node metastasis from breast cancer tissue is 93.33%, while the positive rate of expression without the lymph node metastasis is 66.67%. The expression of mTOR has clear correlations with infiltrating degree of breast cancer and lymph node metastasis (P0.05).4. mTOR protein expression and eIF4E protein expression are positively related (P <0.05). 5. The mTOR protein expression and 4EBPS protein expression is inversely related (P<0.05).6.4EBPS protein expression and eIF4E. protein expression is inversely related (P< 0.05).Conclusion:1. The positive expression rates of mTOR and eIF4E in the breast cancer tissue are higher than those in the normal breast tissue. The positive rate of 4EBPS protein in the breast cancer tissue is obviously lower than that in the normal breast tissue. All those show that the abnormal expression of these three proteins may relate with the incidence of breast cancer.2. The positive rate of expression of eIF4E and mTOR in the lymph node metastasis from breast cancer tissue is higher than those without the lymph node metastasis from breast cancer tissue. There is no clear differentiation of the positive rate of expression of 4EBPS protein between with and without lymph node metastasis. All those show that the abnormal expression of these three proteins may relate with the metastasis of breast cancer.3. The positive rates of expression of eIF4E,4EBPS and mTOR are all related with each other, which show that there is an internal relation among these three proteins in the process of incidence of breast cancer.