Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 Oct;85(8):1211–1218. doi: 10.1054/bjoc.2001.2053

Profile of differentially expressed genes mediated by the type III epidermal growth factor receptor mutation expressed in a small-cell lung cancer cell line

M W Pedersen 1,1, T Thykjær 2, T F Ørntoft 2, L Damstrup 1,1, H S Poulsen 1,1
PMCID: PMC2375145  PMID: 11710837

Abstract

Previous studies have shown a correlation between expression of the EGF receptor type III mutation (EGFRvIII) and a more malignant phenotype of various cancers including: non-small-cell lung cancer, glioblastoma multiforme, prostate cancer and breast cancer. Thus, a detailed molecular genetic understanding of how the EGFRvIII contributes to the malignant phenotype is of major importance for future therapy. The GeneChip Hu6800Set developed by Affymetrix was used to identify changes in gene expression caused by the expression of EGFRvIII. The cell line selected for the study was an EGF receptor negative small-cell-lung cancer cell line, GLC3, stably transfected with the EGFRvIII gene in a Tet-On system. By comparison of mRNA levels in EGFRvIII-GLC3 with those of Tet-On-GLC3, it was found that the levels of mRNAs encoding several transcription factors (ATF-3, JunD, and c-Myb), cell adhesion molecules (CD36, CD24), signal transduction related molecules (MKP-1) and other molecules related to cancer (CD98, thymosin beta-10) were altered in the EGFRvIII transfected cell line. Northern hybridisations and Western blot analyses were used to verify selected results. The results indicate that expression of EGFRvIII alters expression of genes involved in the control of cell growth, survival and motility. © 2001 Cancer Research Campaign  http://www.bjcancer.com

Keywords: EGFRvIII, profile, gene, expression

Full Text

The Full Text of this article is available as a PDF (106.4 KB).

Footnotes

Supported by the Danish Cancer Society and the Danish Research Council

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antonyak M. A., Moscatello D. K., Wong A. J. Constitutive activation of c-Jun N-terminal kinase by a mutant epidermal growth factor receptor. J Biol Chem. 1998 Jan 30;273(5):2817–2822. doi: 10.1074/jbc.273.5.2817. [DOI] [PubMed] [Google Scholar]
  2. Batra S. K., Castelino-Prabhu S., Wikstrand C. J., Zhu X., Humphrey P. A., Friedman H. S., Bigner D. D. Epidermal growth factor ligand-independent, unregulated, cell-transforming potential of a naturally occurring human mutant EGFRvIII gene. Cell Growth Differ. 1995 Oct;6(10):1251–1259. [PubMed] [Google Scholar]
  3. Brinckerhoff C. E., Rutter J. L., Benbow U. Interstitial collagenases as markers of tumor progression. Clin Cancer Res. 2000 Dec;6(12):4823–4830. [PubMed] [Google Scholar]
  4. Der S. D., Zhou A., Williams B. R., Silverman R. H. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15623–15628. doi: 10.1073/pnas.95.26.15623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Garcia de Palazzo I. E., Adams G. P., Sundareshan P., Wong A. J., Testa J. R., Bigner D. D., Weiner L. M. Expression of mutated epidermal growth factor receptor by non-small cell lung carcinomas. Cancer Res. 1993 Jul 15;53(14):3217–3220. [PubMed] [Google Scholar]
  6. Kaminski N., Allard J. D., Pittet J. F., Zuo F., Griffiths M. J., Morris D., Huang X., Sheppard D., Heller R. A. Global analysis of gene expression in pulmonary fibrosis reveals distinct programs regulating lung inflammation and fibrosis. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1778–1783. doi: 10.1073/pnas.97.4.1778. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lorimer I. A., Lavictoire S. J. Activation of extracellular-regulated kinases by normal and mutant EGF receptors. Biochim Biophys Acta. 2001 Feb 5;1538(1):1–9. doi: 10.1016/s0167-4889(00)00129-4. [DOI] [PubMed] [Google Scholar]
  8. Moscatello D. K., Holgado-Madruga M., Emlet D. R., Montgomery R. B., Wong A. J. Constitutive activation of phosphatidylinositol 3-kinase by a naturally occurring mutant epidermal growth factor receptor. J Biol Chem. 1998 Jan 2;273(1):200–206. doi: 10.1074/jbc.273.1.200. [DOI] [PubMed] [Google Scholar]
  9. Moscatello D. K., Holgado-Madruga M., Godwin A. K., Ramirez G., Gunn G., Zoltick P. W., Biegel J. A., Hayes R. L., Wong A. J. Frequent expression of a mutant epidermal growth factor receptor in multiple human tumors. Cancer Res. 1995 Dec 1;55(23):5536–5539. [PubMed] [Google Scholar]
  10. Nagane M., Coufal F., Lin H., Bögler O., Cavenee W. K., Huang H. J. A common mutant epidermal growth factor receptor confers enhanced tumorigenicity on human glioblastoma cells by increasing proliferation and reducing apoptosis. Cancer Res. 1996 Nov 1;56(21):5079–5086. [PubMed] [Google Scholar]
  11. Nagane M., Levitzki A., Gazit A., Cavenee W. K., Huang H. J. Drug resistance of human glioblastoma cells conferred by a tumor-specific mutant epidermal growth factor receptor through modulation of Bcl-XL and caspase-3-like proteases. Proc Natl Acad Sci U S A. 1998 May 12;95(10):5724–5729. doi: 10.1073/pnas.95.10.5724. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Nishikawa R., Ji X. D., Harmon R. C., Lazar C. S., Gill G. N., Cavenee W. K., Huang H. J. A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7727–7731. doi: 10.1073/pnas.91.16.7727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Olapade-Olaopa E. O., Moscatello D. K., MacKay E. H., Horsburgh T., Sandhu D. P., Terry T. R., Wong A. J., Habib F. K. Evidence for the differential expression of a variant EGF receptor protein in human prostate cancer. Br J Cancer. 2000 Jan;82(1):186–194. doi: 10.1054/bjoc.1999.0898. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Prigent S. A., Lemoine N. R. The type 1 (EGFR-related) family of growth factor receptors and their ligands. Prog Growth Factor Res. 1992;4(1):1–24. doi: 10.1016/0955-2235(92)90002-y. [DOI] [PubMed] [Google Scholar]
  15. Sugawa N., Yamamoto K., Ueda S., Morita N., Kita M., Nishino H., Fushiki S., Okabe T. Function of aberrant EGFR in malignant gliomas. Brain Tumor Pathol. 1998;15(1):53–57. doi: 10.1007/BF02482101. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES