Skip to main content

Advertisement

SpringerLink
Log in

Network motifs in the transcriptional regulation network of cervical carcinoma cells respond to EGF

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Cervical carcinoma is the second most prevalent and the fifth most deadly malignancy seen in women worldwide. Dysregulated activation of EGF ErbB system has been implicated in diverse types of human cancer; however, it is elusive how it is regulated in human cervical cancer cells. We herein aimed to explore the mechanisms of cervical carcinoma response to epidermal growth factor (EGF), with a view of the pathways activated by EGF.

Methods

Using the GSE6783 affymetrix microarray data accessible from gene expression omnibus database, we first identified the differentially expressed genes between EGF-stimulated and -unstimulated samples. Then we constructed a regulation network and identified the network motifs. We also performed biological process and pathway enrichment analyses to functionally classify the genes in the regulation network.

Results

A total of 11 network motifs were identified in the regulation network. EGF treatment could increase the risk of cancer via dysregulation of cancer-related pathways and immune response pathways.

Conclusions

Network motif analysis is useful in mining the useful information underlying the network. We hope our work could serve as a basis for further experimentation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Armstrong EP (2010) Prophylaxis of cervical cancer and related cervical disease: a review of the cost-effectiveness of vaccination against oncogenic HPV types. J Manag Care Pharm 16(3):217–230

    PubMed  Google Scholar 

  2. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics. CA Cancer J Clin 59(4):225–249. doi:10.3322/caac.20006

    Article  PubMed  Google Scholar 

  3. Einstein MH, Schiller JT, Viscidi RP, Strickler HD, Coursaget P, Tan T, Halsey N, Jenkins D (2009) Clinician’s guide to human papillomavirus immunology: knowns and unknowns. Lancet Infect Dis 9(6):347–356. doi:10.1016/S1473-3099(09)70108-2

    Article  PubMed  CAS  Google Scholar 

  4. Brake T, Lambert PF (2005) Estrogen contributes to the onset, persistence, and malignant progression of cervical cancer in a human papillomavirus-transgenic mouse model. Proc Natl Acad Sci USA 102(7):2490–2495. doi:10.1073/pnas.0409883102

    Article  PubMed  CAS  Google Scholar 

  5. Herbst RS (2004) Review of epidermal growth factor receptor biology. Int J Radiat Oncol Biol Phys 59(2):21–26. doi:10.1016/j.ijrobp.2003.11.041

    Article  PubMed  CAS  Google Scholar 

  6. Levin ER (2003) Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol Endocrinol 17(3):309–317. doi:10.1210/me.2002-0368me.2002-0368

    Article  PubMed  CAS  Google Scholar 

  7. Vignon F, Bouton MM, Rochefort H (1987) Antiestrogens inhibit the mitogenic effect of growth factors on breast cancer cells in the total absence of estrogens. Biochem Biophys Res Commun 146(3):1502–1508, pii: 0006-291X(87)90819-9

    Article  PubMed  CAS  Google Scholar 

  8. Yarden Y, Sliwkowski MX (2001) Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2(2):127–137. doi:10.1038/35052073

    Article  PubMed  CAS  Google Scholar 

  9. Hynes NE, Lane HA (2005) ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer 5(5):341–354. doi:10.1038/nrc1609

    Article  PubMed  CAS  Google Scholar 

  10. Mangan S, Alon U (2003) Structure and function of the feed-forward loop network motif. Proc Natl Acad Sci USA 100(21):11980–11985. doi:10.1073/pnas.21338411002133841100

    Article  PubMed  CAS  Google Scholar 

  11. Milo R, Shen-Orr S, Itzkovitz S, Kashtan N, Chklovskii D, Alon U (2002) Network motifs: simple building blocks of complex networks. Science 298(5594):824–827. doi:10.1126/science.298.5594.824298/5594/824

    Article  PubMed  CAS  Google Scholar 

  12. Han JD, Bertin N, Hao T, Goldberg DS, Berriz GF, Zhang LV, Dupuy D, Walhout AJ, Cusick ME, Roth FP, Vidal M (2004) Evidence for dynamically organized modularity in the yeast protein–protein interaction network. Nature 430(6995):88–93. doi:10.1038/nature02555nature02555

    Article  PubMed  CAS  Google Scholar 

  13. Jeong H, Mason SP, Barabasi AL, Oltvai ZN (2001) Lethality and centrality in protein networks. Nature 411(6833):41–42. doi:10.1038/3507513835075138

    Article  PubMed  CAS  Google Scholar 

  14. Jaimovich A, Elidan G, Margalit H, Friedman N (2006) Towards an integrated protein–protein interaction network: a relational Markov network approach. J Comput Biol 13(2):145–164. doi:10.1089/cmb.2006.13.145

    Article  PubMed  CAS  Google Scholar 

  15. Jeong H, Tombor B, Albert R, Oltvai ZN, Barabasi AL (2000) The large-scale organization of metabolic networks. Nature 407(6804):651–654. doi:10.1038/35036627

    Article  PubMed  CAS  Google Scholar 

  16. Amit I, Citri A, Shay T, Lu Y, Katz M, Zhang F, Tarcic G, Siwak D, Lahad J, Jacob-Hirsch J, Amariglio N, Vaisman N, Segal E, Rechavi G, Alon U, Mills GB, Domany E, Yarden Y (2007) A module of negative feedback regulators defines growth factor signaling. Nat Genet 39(4):503–512. doi:10.1038/ng1987

    Article  PubMed  CAS  Google Scholar 

  17. Matys V, Fricke E, Geffers R, Gossling E, Haubrock M, Hehl R, Hornischer K, Karas D, Kel AE, Kel-Margoulis OV, Kloos DU, Land S, Lewicki-Potapov B, Michael H, Munch R, Reuter I, Rotert S, Saxel H, Scheer M, Thiele S, Wingender E (2003) TRANSFAC: transcriptional regulation, from patterns to profiles. Nucl Acids Res 31(1):374–378

    Article  PubMed  CAS  Google Scholar 

  18. Jiang C, Xuan Z, Zhao F, Zhang MQ (2007) TRED: a transcriptional regulatory element database, new entries and other development. Nucl Acids Res 35:D137–D140. doi:10.1093/nar/gkl1041

    Article  PubMed  CAS  Google Scholar 

  19. Smyth GK (2004) Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3 (3). doi:10.2202/1544-6115.1027

  20. Derrick TR, Bates BT, Dufek JS (1994) Evaluation of time-series data sets using the Pearson product-moment correlation coefficient. Med Sci Sports Exerc 26(7):919–928

    PubMed  CAS  Google Scholar 

  21. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T (2003) Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 13(11):2498–2504. doi:10.1101/gr.123930313/11/2498

    Article  PubMed  CAS  Google Scholar 

  22. Wernicke S, Rasche F (2006) Fanmod: a tool for fast network motif detection. Bioinformatics 22(9):1152–1153. doi:10.1093/bioinformatics/btl038

    Article  PubMed  CAS  Google Scholar 

  23. da Huang W, Sherman BT, Lempicki RA (2009) Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4(1):44–57. doi:10.1038/nprot.2008.211

    Article  CAS  Google Scholar 

  24. Brake T, Connor JP, Petereit DG, Lambert PF (2003) Comparative analysis of cervical cancer in women and in a human papillomavirus-transgenic mouse model: identification of minichromosome maintenance protein 7 as an informative biomarker for human cervical cancer. Cancer Res 63(23):8173–8180

    PubMed  CAS  Google Scholar 

  25. Mangan S, Zaslaver A, Alon U (2003) The coherent feedforward loop serves as a sign-sensitive delay element in transcription networks. J Mol Biol 334(2):197–204, pii: S0022283603012038

    Article  PubMed  CAS  Google Scholar 

  26. Zaslaver A, Mayo AE, Rosenberg R, Bashkin P, Sberro H, Tsalyuk M, Surette MG, Alon U (2004) Just-in-time transcription program in metabolic pathways. Nat Genet 36(5):486–491. doi:10.1038/ng1348ng1348

    Article  PubMed  CAS  Google Scholar 

  27. Lo RS, Wotton D, Massague J (2001) Epidermal growth factor signaling via ras controls the smad transcriptional co-repressor TGIF. EMBO J 20(1–2):128–136. doi:10.1093/emboj/20.1.128

    Article  PubMed  CAS  Google Scholar 

  28. Derynck R, Zhang YE (2003) Smad-dependent and smad-independent pathways in TGF-beta family signalling. Nature 425(6958):577–584. doi:10.1038/nature02006

    Article  PubMed  CAS  Google Scholar 

  29. Lee HP, Seo SS (2002) The application of human papillomavirus testing to cervical cancer screening. Yonsei Med J 43(6):763–768

    PubMed  Google Scholar 

  30. Li L, He S, Sun JM, Davie JR (2004) Gene regulation by Sp1 and Sp3. Biochem Cell Biol 82(4):460–471. doi:10.1139/o04-045o04-045

    Article  PubMed  CAS  Google Scholar 

  31. Wang LW, Li Q, Hua ZL, Zhou F, Keping X, Daoyan W, Yao J, Ajani J (2007) Expression of transcription factor Sp1 in human gastric cancer tissue and its correlation with prognosis. Zhonghua Zhong Liu Za Zhi 29(2):107–111

    PubMed  CAS  Google Scholar 

  32. Wang F, Li Y, Zhou J, Xu J, Peng C, Ye F, Shen Y, Lu W, Wan X, Xie X (2011) miR-375 is down-regulated in squamous cervical cancer and inhibits cell migration and invasion via targeting transcription factor SP1. Am J Pathol 179(5):2580–2588. doi:10.1016/j.ajpath.2011.07.037

    Article  PubMed  CAS  Google Scholar 

  33. Cho S, Cinghu S, Yu JR, Park WY (2011) Helicase-like transcription factor confers radiation resistance in cervical cancer through enhancing the DNA damage repair capacity. J Cancer Res Clin Oncol 137(4):629–637. doi:10.1007/s00432-010-0925-5

    Article  PubMed  CAS  Google Scholar 

  34. Leslie MC, Bar-Eli M (2005) Regulation of gene expression in melanoma: new approaches for treatment. J Cell Biochem 94(1):25–38. doi:10.1002/jcb.20296

    Article  PubMed  CAS  Google Scholar 

  35. Papassava P, Gorgoulis VG, Papaevangeliou D, Vlahopoulos S, van Dam H, Zoumpourlis V (2004) Overexpression of activating transcription factor-2 is required for tumor growth and progression in mouse skin tumors. Cancer Res 64(23):8573–8584. doi:10.1158/0008-5472.CAN-03-0955

    Article  PubMed  CAS  Google Scholar 

  36. Vlahopoulos SA, Logotheti S, Mikas D, Giarika A, Gorgoulis V, Zoumpourlis V (2008) The role of ATF-2 in oncogenesis. Bioessays 30(4):314–327. doi:10.1002/bies.20734

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was funded (in part) by Shanghai Science and Technology Committee Foundation, grant number [09411962500]. This study was funded (in part) by Shanghai Municipal Health Bureau Foundation, grant number [054019]. This study was funded (in part) by Foundation from The first People’s Hospital, Shanghai Jiaotong University, grant number [06B27].

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Shanghai First People Hospital, Shanghai Jiaotong University, No.100 Haining Road, Hongkou District, 200080, Shanghai, China

    Su Fang Wu, Wen Yan Qian, Jia Wen Zhang, Yong Bin Yang, Yuan Liu, Yu Dong, Zhen Bo Zhang, Ya Ping Zhu & You Ji Feng

Authors
  1. Su Fang Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wen Yan Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jia Wen Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yong Bin Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yu Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhen Bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ya Ping Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. You Ji Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Su Fang Wu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wu, S.F., Qian, W.Y., Zhang, J.W. et al. Network motifs in the transcriptional regulation network of cervical carcinoma cells respond to EGF. Arch Gynecol Obstet 287, 771–777 (2013). https://doi.org/10.1007/s00404-012-2608-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-012-2608-8

Keywords

Search

Navigation