Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma

Brass, Nicole; Heckel, Dirk; Şahin, Uğur; Pfreundschuh, Michael; Sybrecht, Gerhard W.; Meese, Eckart

doi:10.1093/hmg/6.1.33

Cited by 118 publications

(60 citation statements)

References 15 publications

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“…In addition, eukaryotic translation initiation factor 4 (eIF4), which is involved in protein translation, is a SEREX-defined antigen in lung cancer. It has been shown that its immunogenicity is due to overexpression (Brass et al, 1997). We speculate that the proteins identified here generate autoimmune reactions through similar mechanisms.…”

Section: Discussionsupporting

confidence: 55%

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

et al. 2002

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Serological screening of recombinant cDNA expression libraries has been widely used for the identification of tumour antigens in various cancer types. Identification of tumour antigens in ovarian cancer may facilitate the development of vaccine-based therapies and of disease biomarkers. The purpose of our investigation is to identify tumour antigens in ovarian cancer by using the serological analysis of recombinant cDNA expression libraries method. A recombinant ovarian carcinoma cDNA expression library was screened with ascites fluid, pooled from five ovarian cancer patients. Twelve tumour antigens encoded by known genes were isolated, including ribosomal protein S18, heat shock protein 90, JK-recombination signal binding protein, ribonucleoprotein H1, RAN binding protein 7, TG-interacting factor, eukaryotic translation initiation factor p40 subunit, human amyloid precursor protein-binding protein 1, ribosomal protein L8, CDC23, IQ motif containing GTPase activating protein 1, and ribosomal protein L3. Heat shock protein 90 was chosen for further investigation. The prevalence of hsp90 autoantibodies in ovarian cancer was determined with immunoassay. Sera from 22 normal females, 32 from ovarian cancer (22 stage III/IV, 10 stage I/II), 37 colorectal cancer, 13 breast cancer, 10 lung cancer, 20 benign gynaecologic diseases, and 10 benign breast lesions were screened. Seven (32%) stage III/IV ovarian cancer, 1 (10%) stage I/II ovarian cancer, 1 (3%) colorectal cancer, 1 (8%) breast cancer, and 1 (5%) benign gynaecologic disease sera were found to contain hsp90 autoantibodies. These data support the view that hsp90 autoantibodies are frequently found in late stage ovarian cancer. Hsp90 may, therefore, represent a novel biomarker for ovarian cancer and a candidate ovarian cancer vaccine target.

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Section: Discussionsupporting

confidence: 55%

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

et al. 2002

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“…5,19 In previously published studies, we detected an amplification of the eIF4G-1 gene in 30% of the squamous cell carcinomas of the lung. 10 Here, we first show an overexpression of the eIF4G-1 protein in solid tumors. There is no correlation between the elevated expression level of eIF4G-1 and the TNM staging of the lung carcinomas.…”

Section: Discussionmentioning

confidence: 79%

“…The eIF4G-1 gene is located within this region, and we proved that there is an amplification of this translational factor in SCC of the lung. 10 SCC belongs to the group of nonsmall cell lung carcinomas (NSCLC), which represents 75-80% of all lung tumors with only 10% long-term survivors. 11,12 These data and the variety of studies concerning overexpression of translational factors in cancer lead us to this study.…”

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confidence: 99%

Overexpression of the eukaryotic translation initiation factor 4G (eIF4G‐1) in squamous cell lung carcinoma

Bauer

Brass

Diesinger

et al. 2001

Intl Journal of Cancer

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eIF4G-1 belongs to the family of translational initiation factors and is recognized as the central organizing protein in recruitment of mRNA during translational initiation. Previously published studies have provided some evidence that overexpression of translational factors is a general event in the process of carcinogenesis. We have characterized the expression of the eIF4G-1 protein in 33 squamous cell carcinoma (SCC) of the lung by Western blotting. Overexpression of the eIF4G-1 protein was detected in 61% of the tumors compared to the respective normal lung tissue. In addition, we analyzed the expression of this protein by immunohistochemistry in 138 SCC of the lung using a newly generated antibody that is specific for eIF4G-1 as determined by Western blotting. This anti-eIF4G-1 antibody was suitable for the immunohistochemistry of paraffin-embedded tissues. There is a strong cytoplasmic staining detected in the tumor areas that is consistent with the cytoplasmic localization of the translation factor eIF4G-1. In 72% of the examined tissue sections of SCCs of the lung, we detected an overexpression of the eIF4G-1 protein compared to the surrounding connective tissue. Two tumors that were analyzed by both methods showed an overexpression of eIF4G-1 both with Western blot analysis and immunohistochemical staining. Overexpression of eIF4G-1 may result in an increased amount of the translation initiation complex eIF4F, which in turn may activate the translation of the same target mRNAs as eIF4E. © 2002 Wiley-Liss, Inc. Key words: eIF4G; expression; squamous cell lung carcinomaTranslational initiation factors are involved in mRNA recruitment to the 43S initiation complex. A variety of previously published studies have shown that translational initiaton factors, in particularly the cap-binding protein eIF4E, are involved in the process of carcinogenesis. Overexpression of eIF4E resulted in cell transformation as shown for NIH3T3, CHO or REF. A transformed phenotype can include morphologic changes or shortening of generation time. 1 It is additionally described that eIF4E is overexpressed in different tumor types. The highest eIF4E elevation was found in breast cancer as demonstrated by an overexpression of this protein using Western blot analysis and immunohistochemical staining techniques. 2 Also in colon carcinomas and in head and neck squamous cell carcinomas, an elevated eIF4E expression was detected. 1,3 Further studies have shown that there is an increased expression of the initiation factors 4E and 2alpha in lymphomas and a correlation to the biologic aggressiveness. 4 Other members belonging to the family of translational initiation factors include eIF3, eIF4A and eIF4G. There are 2 isoforms of eIF4G in mammals: eIF4G-1 and eIF4G-2. The molecular masses range from 154 kDa to 220 kDa and have 46% identity at the amino acid level. 5-8 The eIF4G-1 translational factor forms with 2 other factors, termed eIF4E and eIF4A, a large protein complex called eIF4F. eIF4G-1 has binding sites for these 2 factors, for t...

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“…Several previously known cytotoxic T cell targets, for example tyrosinase and MAGE antigens, have been detected by SEREX, supporting the premise of integrated CTL and B cell responses to tumour antigens. Moreover, antibody responses to mutated p53 (Scanlan et al, 1998), putative tumour suppressor ING1 and amplified translation factor eIF-g4 (Brass et al, 1997) have been detected by SEREX, thus demonstrating the potential of this technique for identification of genes that play a role in cancer aetiology and may serve as diagnostic markers or indicators of progression of the disease.…”

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confidence: 95%

Serological identification and expression analysis of gastric cancer-associated genes

et al. 2002

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Serological identification of tumour antigens by recombinant expression cloning has proved to be an effective strategy for the identification of cancer-associated genes having a relevance to cancer aetiology and progression, and for defining possible targets for immunotherapeutic intervention. In the present study we applied this technique to identify immunogenic proteins for gastric cancer that resulted in isolation of 14 distinct serum-reactive antigens. In order to evaluate their role in tumourigenesis and assess the immunogenicity of the identified antigens, we characterised each cDNA clone by DNA sequence analysis, mRNA tissue distribution, comparison of mRNA levels in cancerous and adjacent non-cancerous tissues and the frequency of antibody responses in allogeneic patient and control sera. Previously unknown splice variants of TACC1 and an uncharacterised gene Ga50 were identified. The expression of a newly identified TACC1 isoform is restricted to brain and gastric cancer tissues. Comparison of mRNA levels by semi-quantitative RT -PCR revealed a relative overexpression of three genes in cancer tissues, including growth factor granulin and Tbdn-1 -an orthologue of the mouse acetyltransferase gene which is associated with blood vessel development. An unusual DNA polymorphism -a three-nucleotide deletion was found in NUCB2 cDNA but its mRNA level was consistently decreased in gastric tumours compared with that in the adjacent noncancerous tissues. This study has revealed several new gastric cancer candidate genes; additional studies are required to gain a deeper insight into their role in the tumorigenesis and their potential as therapeutic targets.

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Translation initiation factor eIF-4gamma is encoded by an amplified gene and induces an immune response in squamous cell lung carcinoma

Cited by 118 publications

References 15 publications

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

Identification of heat shock protein 90 and other proteins as tumour antigens by serological screening of an ovarian carcinoma expression library

Overexpression of the eukaryotic translation initiation factor 4G (eIF4G‐1) in squamous cell lung carcinoma

Serological identification and expression analysis of gastric cancer-associated genes

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