In Vitro Cellular & Developmental Biology - Animal

, Volume 38, Issue 8, pp 481–486 | Cite as

The effects of epidermal growth factor on gene expression in human fibroblasts

Articles Signal Transduction


A better understanding of the molecular effects of epidermal growth factor (EGF) on target cell can help to reveal important aspects of cellular proliferation, transformation, and apoptosis, as well as embryonic and fetal development. In this study, we examined the differences in gene expression of cultured fibroblasts with EGF stimulation for 48 h by using high-density complementary deoxyribonucleic acid (cDNA) arrays. We found that EGF could cause widespread alteration in gene expression. Eight hundred and fifty-five genes, more than 20% of those assayed, showed changed expression, which are involved in various cellular processes, such as energetic metabolism, biosynthesis, the progress of cell cycle, and the signaling pathways of receptor tyrosine kinase (RTKs) and G protein-coupled receptors (GPCRs). The most striking finding is that long-term EGF treatment on cultured fibroblasts resulted in down-regulation of the genes encoding membrane receptors and ion channels and desensitized RTKs and GPCRs to their physiological and nonphysiological stimuli, which seems to be a slow-acting, but permanent, effect of EGF on RTK and GPCR signaling pathways and to play important roles in embryonic and fetal development.

Key words

in vitro cDNA array gene expression profile G protein-coupled receptor signaling transduction 


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  1. Brunet, A.; Datta, S. R.; Greenberg, M. E. Transcription-dependent and-independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr. Opin. Neurobiol. 11:297–305; 2001.PubMedCrossRefGoogle Scholar
  2. Carpenter, G.. The EGF receptor: a nexus for trafficking and signaling. Bioessays 22:697–707; 2000.PubMedCrossRefGoogle Scholar
  3. Carpenter, G.; Cohen, S. Epidermal growth factor. Ann. Rev. Biochem. 48:193–216; 1979.PubMedCrossRefGoogle Scholar
  4. Chiechanover, A. The ubiquitin-proteasome proteolytic pathway. Cell 79:13–21; 1995.CrossRefGoogle Scholar
  5. Darnell, J. E., Jr.; Kerr, J. M.; Stark, G. R.. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415–1421; 1994.PubMedCrossRefGoogle Scholar
  6. Hackel, P. O.; Zwick, E.; Prenzel, N. et al. Epidermal growth factor receptors: critical mediators of multiple receptor pathways. Curr. Opin. Cell Biol. 11:177–183; 1999.CrossRefGoogle Scholar
  7. Hadcock, J. R.; Port, J. D.; Gelman, M. S. et al. Cross-talk between tyrosine kinase and G-protein-linked receptors. Phosphorylation of beta 2-adrenergic receptors in response to insulin. J. Biol. Chem. 267:26017–26022; 1992.PubMedGoogle Scholar
  8. Lamm, M. L.; Rajagopalan-Gupta, R. M.; Hunzicker-Dunn, M. Epidermal growth factor-induced heterologous desensitization of the luteinizing hormone/choriogonadotropin receptor in a cell-free membrane preparation is associated with the tyrosine phosphorylation of the epidermal growth factor receptor. Endocrinology 140:29–36; 1999.PubMedCrossRefGoogle Scholar
  9. Leibmann, C.; Graness, A.; Boehmer, A., et al. Tyrosine phosphorylation of GSalpha and inhibition of bradykinin-induced activation of the cyclic AMP pathway in A431 cells by epidermal growth factor receptor. J. Biol. Chem. 271:31098–31105; 1996.CrossRefGoogle Scholar
  10. Li, B. S.; Veeranna; Gu, J., et al. Activation of mitogen-activated protein kinases (Erk1 and Erk2) cascade results in phosphorylation of NFM tail domains in transfected NIH 3T3 cells. Eur. J. Biochem. 262:211–217; 1999.PubMedCrossRefGoogle Scholar
  11. Reddy, K. B. Epidermal growth factor induced apoptosis. Apoptosis 1:33–39; 1996.CrossRefGoogle Scholar
  12. Schena, M.; Schalon, D.; Heller, R. et al. Parallel human genome analysis: microarray-based expression monitoring of 1000 gene. Proc. Natl. Acad. Sci. USA 93:10614–10619; 1996.PubMedCrossRefGoogle Scholar
  13. Sheng, H.; Shao, J.; DuBois, R. N. Akt/PKB activity is required for Ha-Rasmediated transformation of intestinal epithelial cells. J. Biol. Chem. 276:14498–14504; 2001.PubMedGoogle Scholar
  14. Tang, Z. Q.; Zhang, Z. Y.; Zheng, Y. S., et al. Cell aging of human diploid fibroblasts is associated with changes in responsiveness to epidermal growth factor and changes in HER-2 expression. Mech. Ageing Dev. 73:57–67; 1994.PubMedCrossRefGoogle Scholar
  15. Van Golen, C. M.; Schwab, T. S.; Ignatoski, K. M., et al. PTEN/MMAC1 overexpression decreases insulin-like growth factor-I-mediated protection from apoptosis in neuroblastoma cells. Cell Growth Differ. 12:371–378; 2001.PubMedGoogle Scholar
  16. Yamada, M.; Ikeuchi, T.; Hatanaka, H. The neurotrophic action and signalling of epidermal growth factor. Prog. Neurobiol. 51:19–37; 1997.PubMedCrossRefGoogle Scholar
  17. Zastrow, M. V. Endocytosis and downregulation of G protein-coupled receptors. Parkinsonism Relat. Disord. 7:265–271; 2001.CrossRefGoogle Scholar
  18. Zwick, E.; Hackel, P. O.; Prenzel, N., et al. The EGF receptor as central transducer of heterologous signalling systems. Trends Pharmacol. Sci. 20:408–412; 1999.PubMedCrossRefGoogle Scholar

Copyright information

© Society for In Vitro Biology 2002

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Health Science CenterPeking UniversityBeijing

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