Expression And Clinical Significance Of ABCE1 In Human Lung Adenocarcinoma

PrefaceThe ABCE1 gene is a member of the ATP-binding cassette (ABC) multigenefamily and is composed of two nucleotide binding domains and an N-terminal Fe-Sbinding domain. ABCE1 is one of the most highly conserved proteins and is found inone or two copies in all characterized eukaryotes and archaea. The ABCE1 geneencodes a protein originally identified for its inhibition of ribonuclease L, a nucleaseinduced by interferon in mammalian cells. The protein is also required for the assemblyof the HIV and SIV gag polypeptides. Yeast ABCE1 is essential to cell division andinteracts 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 invivo translation of mRNA and that it binds to eIF2 and eIF5. Suppressing ABCE1expression in a human cell line changes the polysome profile, with a decrease in largepolysomes and an increase in 80 S ribosomal subunits. Human anti-ABCE1 antibodyspecifically inhibits mRNA translation. It is known that tumor cells have a highcapacity for protein translation, and proteins involved in translation such as S6 kinase,mTOR, and 4E-BP1 are molecular targets for cancer therapy. ABCE1 inhibitorsefficiently suppress the growth of human tumor cells. It is possible that cancer cells aremore sensitive to inhibition of protein translation through ABCE1 than are normal cells.However, most of these studies are limited to animal models or cultured cell lines invitro, so little is known about the expression of ABCE1 in human, particularly lungcancer tissues in vivo. Our study focused on the expression of ABCE1 at the mRNAand protein levels in human lung adenocarcinoma tissues in vivo and attempted to establish the role played by ABCE1 in human lung cancer genesis and development.Materials and MethodsLung adenocarcinoma tissues and normal lung tissues located approximately 5 cmfrom the cancer sites in different lobes or segments were collected from 48 patientsundergoing surgical resections of lung cancer. After gross pathological examination,each sample was cut into two parts, one part promptly frozen at-70℃for RT-PCRand/or Western Blot, and the other for immediate fixing with 10％neutral bufferedformalin for immunohistochemistry.ResultsThere was a significant overexpression of ABCE1 mRNA and protein in lungadenocarcinoma tissues as compared with lung normal tissues. In lung adenocarcinomatissue, the relative level of ABCE1 mRNA as evaluated by RT-PCR was 1.91±0.23, thelevel of ABCE1 protein as evaluated by Western Blot was 246.64±56.7. In lung normaltissue, the relative level of ABCE1 mRNA was 1.11±0.16, the level of ABCE1 proteinwas 99.36±18.79. The defferences in expression of ABCE1 between the two tissueswere significant (P＜0.05). Furthemore, the over expression of ABCE1 in the lungadenocarcinoma tissues was correlated to stage of tumors. There was strongerexpression in stageⅢthan in stageⅠandⅡtumors (P＜0.05). No statisticallysignificant difference was found among the grade of differentiation of tumors.Immunohistochemistry showed that the expression of ABCE1 protein was localized incytoplasm.ConclusionsThe expression of ABCE1 protein was localized in cytoplasm. The expression ofABCE1 mRNA and protein in lung adenocarcinoma tissues were significantly higherthan that in lung normal tissues, and were closely related to the genesis and P-TNMstages. ABCE1 may be involved in the genesis and development of human lungadenocarcinoma.