The Expression Of ABCE1 Protein In Human Lung Cancer, Adjacent Tissues And Metastatic Lymph Nodes By Western-blot And Immunohistochemistry

PrefaceBackground Primary bronchoginic carcinoma(lung cancer) is the malignant tumororiginates the epithelium mucosae or glandular organ of the bronchus. Incidence rate and death rate are rising rapidly.Since the 1980,s, lung cancer has become the world's highest incidence of malignant tumors.Early diagnosis of lung cancer is very difficult.65% of patients has become advanced stage when they have a clear diagnosis. Relapse and metastasis are themain reasons for its death. Lymph node metastasis is the main way to lung cancer proliferation,but also the main factors to the impact of radical surgery and prognosis. For most of humanmalignant tumor, tumor cells through lymphatic spread to local lymph nodes are animportant indication of the clinical stage. In the tumor matrix of lymph node metastasis,The ABCE1 gene is a member of the ATP-binding cassette (ABC) mμltigene family and is composed of tw nucleotide binding domains and an N-terminal Fe-S binding domain. ABCE1 is one of the most highly conserved proteins and is found in one or two copies in all characterized eukaryotes and archaea. The ABCE1 gene encodes a protein originally identified for its inhibition of ribonuclease L, a nuclease induced by interferon in mammalian cells. The protein is also required for the assembly of the HIV and SIV gag polypeptides. Yeast ABCE1 is essential to cell division and interacts with translation initiation factors in the assembly of the pre-initiation complex. Many studies have shown that the human ABCE1 protein is essential for in vitro and in vivo translation of mRNA and that it binds to eIF2αand eIF5. Suppressing ABCE1 expression in a human cell line changes the polysome profile, with a decrease in large polysomes and an increase in 80 S ribosomal subunits. Human anti-ABCE1 antibody specifically inhibits mRNA translation. It is known that tumor cells have a high capacity for protein translation, and proteins involved in translation such as S6 kinase, mTOR, and 4E-BP1 are molecμlar targets for cancer therapy. ABCE1 inhibitors efficiently suppress the growth of human tumor cells. It is possible that cancer cells are more sensitive to inhibition of protein translation through ABCE1 than are normal cells. However, most of these studies are limited to animal models or cμltured cell lines in vitro, so little is known about the expression of ABCE1 in human, particμlarly lung cancer tissues in vivo. Our study focused on the expression of ABCE1 protein levels in human lung tissues in vivo and attempted to establish the role played by ABCE1 in human lung cancer occurrence and progress.Materials and MethodsLung carcinoma tissues and normal lung tissues located approximately≥5 cm from the cancer sites in different lobes or segments were collected from 18 patients undergoing surgical resections of lung cancer. After gross pathological examination, each sample was cut into two parts, one part promptly frozen at-80℃for Western Blot, and the other for immediate fixing with 10% neutral buffered formalin for immunohistochemistry.Results1.There was a significant overexpression of ABCE1 protein in lung carcinoma tissues as compared with lung normal tissues. In lung carcinoma tissue, the level of ABCE1 protein as evaluated by Western Blot was 1.032±0.510. In lung normal tissue, the level of ABCE1 protein was 0.631±0.619. The defferences in expression of ABCE1 between the two tissues were significant (P<0.05).2. In Metastatic lymphonode the level of ABCE1 protein as evaluated by Western Blot was 1.269±0.755, In lung normal tissue, the level of ABCE1 protein was 0.631±0.619. The defferences in expression of ABCE1 between the two tissues were significant (P<0.05).3. In Metastatic lymphonode the level of ABCE1 protein as evaluated by Western Blot was 1.269±0.755, In lung carcinoma tissue, the level of ABCEl protein as evaluated by Western Blot was 1.032±0.510. The defferences in expression of ABCE1 between the two tissues were significant (P<0.05).4.In adenocarcinoma the the level of ABCE1 protein as evaluated by Western Blot was1.25±0.79, In squamous carcinoma the the level of ABCE1 protein as evaluated by Western Blot was 0.78±0.30, The defferences in expression of ABCEl between the two tissues were significant (P<0.05).5.No statistically significant difference was found among the grade of differentiation of tumors.6.Immunohistochemistry showed that the expression of ABCE1 protein was localized in cytoplasm.Conclusions1. ABCE1 was related with the occurrence and progress of human lung carcinoma.2. The expression of ABCEl protein was localized in cytoplasm.3. Ascertaining the levels of ABCE1 protein may be valuable in evaluating the clinical stage of human lung carcinoma.