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
Keywords: lung cancer; translation initiation; cell growth control, eIF3; p170
Full Text
The Full Text of this article is available as a PDF (229.5 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Asano K., Kinzy T. G., Merrick W. C., Hershey J. W. Conservation and diversity of eukaryotic translation initiation factor eIF3. J Biol Chem. 1997 Jan 10;272(2):1101–1109. doi: 10.1074/jbc.272.2.1101. [DOI] [PubMed] [Google Scholar]
- Asano K., Merrick W. C., Hershey J. W. 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. 1997 Sep 19;272(38):23477–23480. doi: 10.1074/jbc.272.38.23477. [DOI] [PubMed] [Google Scholar]
- Bachmann F., Bänziger R., Burger M. M. Cloning of a novel protein overexpressed in human mammary carcinoma. Cancer Res. 1997 Mar 1;57(5):988–994. [PubMed] [Google Scholar]
- Benne R., Brown-Luedi M. L., Hershey J. W. Protein synthesis initiation factors from rabbit reticulocytes: purification, characterization, and radiochemical labeling. Methods Enzymol. 1979;60:15–35. doi: 10.1016/s0076-6879(79)60005-8. [DOI] [PubMed] [Google Scholar]
- Block K. L., Vornlocher H. P., Hershey J. W. Characterization of cDNAs encoding the p44 and p35 subunits of human translation initiation factor eIF3. J Biol Chem. 1998 Nov 27;273(48):31901–31908. doi: 10.1074/jbc.273.48.31901. [DOI] [PubMed] [Google Scholar]
- Buratti E., Tisminetzky S., Zotti M., Baralle F. E. Functional analysis of the interaction between HCV 5'UTR and putative subunits of eukaryotic translation initiation factor eIF3. Nucleic Acids Res. 1998 Jul 1;26(13):3179–3187. doi: 10.1093/nar/26.13.3179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carbone D. P. The biology of lung cancer. Semin Oncol. 1997 Aug;24(4):388–401. [PubMed] [Google Scholar]
- Chaudhuri J., Chakrabarti A., Maitra U. 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. 1997 Dec 5;272(49):30975–30983. doi: 10.1074/jbc.272.49.30975. [DOI] [PubMed] [Google Scholar]
- Chen G., Burger M. M. p150 expression and its prognostic value in squamous-cell carcinoma of the esophagus. Int J Cancer. 1999 Apr 20;84(2):95–100. doi: 10.1002/(sici)1097-0215(19990420)84:2<95::aid-ijc1>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
- Chi K., Jones D. V., Frazier M. L. Expression of an elongation factor 1 gamma-related sequence in adenocarcinomas of the colon. Gastroenterology. 1992 Jul;103(1):98–102. doi: 10.1016/0016-5085(92)91101-9. [DOI] [PubMed] [Google Scholar]
- De Benedetti A., Harris A. L. eIF4E expression in tumors: its possible role in progression of malignancies. Int J Biochem Cell Biol. 1999 Jan;31(1):59–72. doi: 10.1016/s1357-2725(98)00132-0. [DOI] [PubMed] [Google Scholar]
- Dellas A., Torhorst J., Bachmann F., Bänziger R., Schultheiss E., Burger M. M. Expression of p150 in cervical neoplasia and its potential value in predicting survival. Cancer. 1998 Oct 1;83(7):1376–1383. doi: 10.1002/(sici)1097-0142(19981001)83:7<1376::aid-cncr15>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
- Donzé O., Jagus R., Koromilas A. E., Hershey J. W., Sonenberg N. Abrogation of translation initiation factor eIF-2 phosphorylation causes malignant transformation of NIH 3T3 cells. EMBO J. 1995 Aug 1;14(15):3828–3834. doi: 10.1002/j.1460-2075.1995.tb00052.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fukuchi-Shimogori T., Ishii I., Kashiwagi K., Mashiba H., Ekimoto H., Igarashi K. Malignant transformation by overproduction of translation initiation factor eIF4G. Cancer Res. 1997 Nov 15;57(22):5041–5044. [PubMed] [Google Scholar]
- Georges E., Bradley G., Gariepy J., Ling V. Detection of P-glycoprotein isoforms by gene-specific monoclonal antibodies. Proc Natl Acad Sci U S A. 1990 Jan;87(1):152–156. doi: 10.1073/pnas.87.1.152. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goumans H., Thomas A., Verhoeven A., Voorma H. O., Benne R. The role of eIF-4C in protein synthesis initiation complex formation. Biochim Biophys Acta. 1980 Jun 27;608(1):39–46. doi: 10.1016/0005-2787(80)90131-8. [DOI] [PubMed] [Google Scholar]
- Hann S. R. Regulation and function of non-AUG-initiated proto-oncogenes. Biochimie. 1994;76(9):880–886. doi: 10.1016/0300-9084(94)90190-2. [DOI] [PubMed] [Google Scholar]
- Harbeck R. J., Hoffman A. A., Redecker S., Biundo T., Kurnick J. The isolation and functional activity of polymorphonuclear leukocytes and lymphocytes separated from whole blood on a single percoll density gradient. Clin Immunol Immunopathol. 1982 Jun;23(3):682–690. doi: 10.1016/0090-1229(82)90331-2. [DOI] [PubMed] [Google Scholar]
- Hofmann K., Bucher P. The PCI domain: a common theme in three multiprotein complexes. Trends Biochem Sci. 1998 Jun;23(6):204–205. doi: 10.1016/s0968-0004(98)01217-1. [DOI] [PubMed] [Google Scholar]
- Johnson K. R., Merrick W. C., Zoll W. L., Zhu Y. 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. 1997 Mar 14;272(11):7106–7113. doi: 10.1074/jbc.272.11.7106. [DOI] [PubMed] [Google Scholar]
- Kalemkerian G. P. Biology of lung cancer. Curr Opin Oncol. 1994 Mar;6(2):147–155. doi: 10.1097/00001622-199403000-00006. [DOI] [PubMed] [Google Scholar]
- Kho C. J., Wang Y., Zarbl H. Effect of decreased fte-1 gene expression on protein synthesis, cell growth, and transformation. Cell Growth Differ. 1996 Sep;7(9):1157–1166. [PubMed] [Google Scholar]
- Lamphear B. J., Kirchweger R., Skern T., Rhoads R. E. 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. 1995 Sep 15;270(37):21975–21983. doi: 10.1074/jbc.270.37.21975. [DOI] [PubMed] [Google Scholar]
- Lazaris-Karatzas A., Montine K. S., Sonenberg N. Malignant transformation by a eukaryotic initiation factor subunit that binds to mRNA 5' cap. Nature. 1990 Jun 7;345(6275):544–547. doi: 10.1038/345544a0. [DOI] [PubMed] [Google Scholar]
- Lew Y., Jones D. V., Mars W. M., Evans D., Byrd D., Frazier M. L. Expression of elongation factor-1 gamma-related sequence in human pancreatic cancer. Pancreas. 1992;7(2):144–152. doi: 10.1097/00006676-199203000-00003. [DOI] [PubMed] [Google Scholar]
- Meyer L. J., Brown-Luedi M. L., Corbett S., Tolan D. R., Hershey J. W. The purification and characterization of multiple forms of protein synthesis eukaryotic initiation factors 2, 3, and 5 from rabbit reticulocytes. J Biol Chem. 1981 Jan 10;256(1):351–356. [PubMed] [Google Scholar]
- Meyer L. J., Milburn S. C., Hershey J. W. Immunochemical characterization of mammalian protein synthesis initiation factors. Biochemistry. 1982 Aug 31;21(18):4206–4212. doi: 10.1021/bi00261a003. [DOI] [PubMed] [Google Scholar]
- Méthot N., Rom E., Olsen H., Sonenberg N. 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. 1997 Jan 10;272(2):1110–1116. doi: 10.1074/jbc.272.2.1110. [DOI] [PubMed] [Google Scholar]
- Méthot N., Song M. S., Sonenberg N. 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. 1996 Oct;16(10):5328–5334. doi: 10.1128/mcb.16.10.5328. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nagase T., Seki N., Tanaka A., Ishikawa K., Nomura N. 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. DNA Res. 1995 Aug 31;2(4):167-74, 199-210. doi: 10.1093/dnares/2.4.167. [DOI] [PubMed] [Google Scholar]
- Naranda T., MacMillan S. E., Hershey J. W. Purified yeast translational initiation factor eIF-3 is an RNA-binding protein complex that contains the PRT1 protein. J Biol Chem. 1994 Dec 23;269(51):32286–32292. [PubMed] [Google Scholar]
- Nupponen N. N., Porkka K., Kakkola L., Tanner M., Persson K., Borg A., Isola J., Visakorpi T. Amplification and overexpression of p40 subunit of eukaryotic translation initiation factor 3 in breast and prostate cancer. Am J Pathol. 1999 Jun;154(6):1777–1783. doi: 10.1016/S0002-9440(10)65433-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pascual J., Castresana J., Saraste M. Evolution of the spectrin repeat. Bioessays. 1997 Sep;19(9):811–817. doi: 10.1002/bies.950190911. [DOI] [PubMed] [Google Scholar]
- Pogue-Geile K., Geiser J. R., Shu M., Miller C., Wool I. G., Meisler A. I., Pipas J. M. Ribosomal protein genes are overexpressed in colorectal cancer: isolation of a cDNA clone encoding the human S3 ribosomal protein. Mol Cell Biol. 1991 Aug;11(8):3842–3849. doi: 10.1128/mcb.11.8.3842. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Riordan J. R., Ling V. Purification of P-glycoprotein from plasma membrane vesicles of Chinese hamster ovary cell mutants with reduced colchicine permeability. J Biol Chem. 1979 Dec 25;254(24):12701–12705. [PubMed] [Google Scholar]
- Scholler J. K., Kanner S. B. The human p167 gene encodes a unique structural protein that contains centrosomin A homology and associates with a multicomponent complex. DNA Cell Biol. 1997 Apr;16(4):515–531. doi: 10.1089/dna.1997.16.515. [DOI] [PubMed] [Google Scholar]
- Tatsuka M., Mitsui H., Wada M., Nagata A., Nojima H., Okayama H. Elongation factor-1 alpha gene determines susceptibility to transformation. Nature. 1992 Sep 24;359(6393):333–336. doi: 10.1038/359333a0. [DOI] [PubMed] [Google Scholar]
- Trachsel H., Erni B., Schreier M. H., Staehelin T. Initiation of mammalian protein synthesis. II. The assembly of the initiation complex with purified initiation factors. J Mol Biol. 1977 Nov;116(4):755–767. doi: 10.1016/0022-2836(77)90269-8. [DOI] [PubMed] [Google Scholar]
- Valásek L., Trachsel H., Hasek J., Ruis H. Rpg1, the Saccharomyces cerevisiae homologue of the largest subunit of mammalian translation initiation factor 3, is required for translational activity. J Biol Chem. 1998 Aug 14;273(33):21253–21260. doi: 10.1074/jbc.273.33.21253. [DOI] [PubMed] [Google Scholar]
- Willis A. E. Translational control of growth factor and proto-oncogene expression. Int J Biochem Cell Biol. 1999 Jan;31(1):73–86. doi: 10.1016/s1357-2725(98)00133-2. [DOI] [PubMed] [Google Scholar]
- Zhang J. T., Ling V. Study of membrane orientation and glycosylated extracellular loops of mouse P-glycoprotein by in vitro translation. J Biol Chem. 1991 Sep 25;266(27):18224–18232. [PubMed] [Google Scholar]
- Zhang M., Wang G., Shapiro A., Zhang J. T. Topological folding and proteolysis profile of P-glycoprotein in membranes of multidrug-resistant cells: implications for the drug-transport mechanism. Biochemistry. 1996 Jul 30;35(30):9728–9736. doi: 10.1021/bi960400s. [DOI] [PubMed] [Google Scholar]
- Zhou J., Mulshine J. L., Unsworth E. J., Scott F. M., Avis I. M., Vos M. D., Treston A. M. 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. 1996 May 3;271(18):10760–10766. doi: 10.1074/jbc.271.18.10760. [DOI] [PubMed] [Google Scholar]
