Abstract
Lung cancer is the leading cause for cancer death in both male and female populations. Although many molecular markers for lung cancer have been developed and useful for early detection of lung cancer, their function remains unknown. In this paper, we report our findings that a 170-kDa protein (p170) is over-expressed in all types of human lung cancers compared with normal tissues and it is identified as a subunit of translation initiation factor eIF3 by cDNA cloning. Translation initiation factors are a family of proteins that promote the initiation step of protein synthesis and are regulators of cell growth at the translational level. Further studies showed that p170 mRNA is ubiquitously expressed with higher levels in adult proliferating tissues (e.g. bone marrow) and tissues during development (e.g. fetal tissues). This study suggests that p170 and eIF3 may be important factors for cell growth, development, and tumorigenesis. © 2001 Cancer Research Campaign http://www.bjcancer.com
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References
Asano K, Kinzy TG, Merrick WC and Hershey JW (1997a) Conservation and diversity of eukaryotic translation initiation factor eIF3. J Biol Chem 272: 1101–1109
Asano K, Merrick WC and Hershey JW (1997b) The translation initiation factor eIF3-p48 subunit is encoded by int-6, a site of frequent integration by the mouse mammary tumor virus genome. J Biol Chem 272: 23477–23480
Bachmann F, Banziger R and Burger MM (1997) Cloning of a novel protein overexpressed in human mammary carcinoma. Cancer Res 57: 988–994
Benne R, Brown-Luedi ML and Hershey JW (1979) Protein synthesis initiation factors from rabbit reticulocytes: purification, characterization, and radiochemical labeling. Methods Enzymol 60: 15–35
Block KL, Vornlocher HP and Hershey JW (1998) Characterization of cDNAs encoding the p44 and p35 subunits of human translation initiation factor eIF3. J Biol Chem 273: 31901–31908
Buratti E, Tisminetzky S, Zotti M and Baralle FE (1998) Functional analysis of the interaction between HCV 5′UTR and putative subunits of eukaryotic translation initiation factor eIF3. Nucleic Acids Res 26: 3179–3187
Carbone DP (1997) The biology of lung cancer. Seminars Oncol 24: 388–401
Chaudhuri J, Chakrabarti A and Maitra U (1997) Biochemical characterization of mammalian translation initiation factor 3 (eIF3). Molecular cloning reveals that p110 subunit is the mammalian homologue of Saccharomyces cerevisiae protein Prt1. J Biol Chem 272: 30975–30983
Chen G and Burger MM (1999) p150 expression and its prognostic value in squamous-cell carcinoma of the esophagus. Int J Cancer 84: 95–100
Chi K, Jones DV and Frazier ML (1992) Expression of an elongation factor I gamma-related sequence in adenocarcinomas of the colon. Gastroenterology 103: 98–102
De Benedetti A and Harris AL (1999) eIF4E expression in tumours: its possible role in progression of malignancies. Int J Biochem Cell Biol 31: 59–72
Dellas A, Torhorst J, Bachmann F, Banziger R, Schultheiss E and Burger MM (1998) Expression of p150 in cervical neoplasia and its potential value in predicting survival. Cancer 83: 1376–1383
Donze O, Jagus R, Koromilas AE, Hershey JW and Sonenberg N (1995) Abrogation of translation initiation factor eIF-2 phosphorylation causes malignant transformation of NIH 3T3 cells. EMBO J 14: 3828–3834
Fukuchi-Shimogori T, Ishii I, Kashiwagi K, Mashiba H, Ekimoto H and Igarashi K (1997) Malignant transformation by overproduction of translation initiation factor eIF4G. Cancer Res 57: 5041–5044
Georges E, Bradley G, Gariepy J and Ling V (1990) Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. Proc Natl Acad Sci 87: 152–156
Goumans H, Thomas A, Verhoeven A, Voorma HO and Benne R (1980) The role of eIF-4C in protein synthesis initiation complex formation. Biochim Biophys Acta 608: 39–46
Hann SR (1994) Regulation and function of non-AUG-initiated proto-oncogenes. Biochim 76: 880–886
Harbeck RJ, Hoffman AA, Redecker S, Biundo T and Kurnick J (1982) The isolation and functional activity of polymorphonuclear leukocytes and lymphocytes separated from whole blood on a single percoll density gradient. Clin Immunol Immunopathol 23: 682–690
Hofmann K and Bucher P (1998) The PCI domain: a common theme in three multiprotein complexes. Trends Biochem Sci 23: 204–205
Johnson KR, Merrick WC, Zoll WL and Zhu Y (1997) Identification of cDNA clones for the large subunit of eukaryotic translation initiation factor 3. Comparison of homologues from human, Nicotiana tabacum, Caenorhabditis elegans, and Saccharomyces cerevisiae. J Biol Chem 272: 7106–7113
Kalemkerian GP (1994) Biology of lung cancer. Curr Opinion Oncol 6: 147–155
Kho CJ, Wang Y and Zarbl H (1996) Effect of decreased fte-1 gene expression on protein synthesis, cell growth, and transformation. Cell Growth Differentiation 7: 1157–1166
Lamphear BJ, Kirchweger R, Skern T and Rhoads RE (1995) Mapping of functional domains in eukaryotic protein synthesis initiation factor 4G (eIF4G) with picornaviral proteases. Implications for cap-dependent and cap-independent translational initiation. J Biol Chem 270: 21975–22183
Lazaris-Karatzas A, Montine KS and Sonenberg N (1990) Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5′ cap. Nature 345: 544–547
Lew Y, Jones DV, Mars WM, Evans D, Byrd D and Frazier ML (1992) Expression of elongation factor-1 gamma-related sequence in human pancreatic cancer. Pancreas 7: 144–152
Methot N, Song MS and Sonenberg N (1996) A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3. Mol Cell Biol 16: 5328–5334
Methot N, Rom E, Olsen H and Sonenberg N (1997) The human homologue of the yeast Prt1 protein is an integral part of the eukaryotic initiation factor 3 complex and interacts with p170. J Biol Chem 272: 1110–1116
Meyer LJ, Brown-Luedi ML, Corbett S, Tolan DR and Hershey JW (1981) The purification and characterization of multiple forms of protein synthesis eukaryotic initiation factors 2, 3, and 5 from rabbit reticulocytes. J Biol Chem 256: 351–356
Meyer LJ, Milburn SC and Hershey JW (1982) Immunochemical characterization of mammalian protein synthesis initiation factors. Biochemistry 21: 4206–4212
Nagase T, Seki N, Tanaka A, Ishikawa K and Nomura N (1995) Prediction of the coding sequences of unidentified human genes. IV. The coding sequences of 40 new genes (KIAA0121-KIAA0160) deduced by analysis of cDNA clones from human cell line KG-1 (supplement). DNA Res 2: 199–210
Naranda T, MacMillan SE and Hershey JW (1994) Purified yeast translational initiation factor eIF-3 is an RNA-binding protein complex that contains the PRT1 protein. J Biol Chem 269: 32286–32292
Nupponen NN, Porkka K, Kakkola L, Tanner M, Persson K, Borg A, Isola J and Visakorpi T (1999) Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer. Am J Pathol 154: 1777–1783
Pascual J, Castresana J and Saraste M (1997) Evolution of the spectrin repeat. Bioessays 19: 811–817
Pogue-Geile K, Geiser JR, Shu M, Miller C, Wool IG, Meisler AI and Pipas JM (1991) Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. Mol Cell Biol 11: 3842–3849
Riordan JR and Ling V (1979) Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. J Biol Chem 254: 12701–12705
Scholler JK and Kanner SB (1997) The human p167 gene encodes a unique structural protein that contains centrosomin A homology and associates with a multicomponent complex. DNA Cell Biol 16: 515–531
Srivastava S and Kramer B (1994) Genetics of lung cancer: Implications for early detection and prevention. In Lung cancer Hansen HH (ed) pp. 91–110. Kluwer Academic Publishers: Norwell
Stahel RA (1995) Monoclonal antibodies to membrane antigens of lung cancer. In Lung cancer D.D, C. (ed) pp. 191–212. Arnold: Lung Cancer
Tatsuka M, Mitsui H, Wada M, Nagata A, Nojima H and Okayama H (1992) Elongation factor-1 alpha gene determines susceptibility to transformation. Nature 359: 333–336
Trachsel H, Erni B, Schreier MH and Staehelin T (1977) Initiation of mammalian protein synthesis. II. The assembly of the initiation complex with purified initiation factors. J Mol Biol 116: 755–767
Valasek L, Trachsel H, Hasek J and Ruis H (1998) Rpg1, the Saccharomyces cerevisiae homologue of the largest subunit of mammalian translation initiation factor 3, is required for translational activity. J Biol Chem 273: 21253–21260
Willis AE (1999) Translational control of growth factor and proto-oncogene expression. Int J Biochem Cell Biol 31: 73–86
Zhang JT and Ling V (1991) Study of membrane orientation and glycosylated extracellular loops of mouse P-glycoprotein by in vitro translation. J Biol Chem 266: 18224–18232
Zhang M, Wang G, Shapiro A and Zhang JT (1996) Topological folding and proteolysis profile of P-glycoprotein in membranes of multidrug-resistant cells: implications for the drug-transport mechanism. Biochemistry 35: 9728–9736
Zhou J, Mulshine JL, Unsworth EJ, Scott FM, Avis IM, Vos MD and Treston AM (1996) Purification and characterization of a protein that permits early detection of lung cancer. Identification of heterogeneous nuclear ribonucleoprotein-A2/B1 as the antigen for monoclonal antibody 703D4. J Biol Chem 271: 10760–10766
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Pincheira, R., Chen, Q. & Zhang, JT. Identification of a 170-kDa protein over-expressed in lung cancers. Br J Cancer 84, 1520–1527 (2001). https://doi.org/10.1054/bjoc.2001.1828
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DOI: https://doi.org/10.1054/bjoc.2001.1828
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