Skip to main content

Malignant Gliomas: Role of E2F1 Transcription Factor

  • Chapter
  • First Online:
Tumors of the Central Nervous System, Volume 1

Part of the book series: Tumors of the Central Nervous System ((TCNS,volume 1))

Abstract

E2F1 is a transcription factor regulated by the Rb pathway. Its role in the G1/S transition and S-phase entry in the cell cycle has been extensively reported. E2F1 regulates the biosynthetic activity of nucleotides, the activation of replication, the progression through M-phase of the cell cycle, and the regulation of genes related with chromosomal stability. In addition to the E2F1 crucial involvement in the cell cycle progression, E2F1 participates in both p53-dependent and independent apoptotic pathways. Our group has previously published the presence of high expression of E2F1 in malignant gliomas and the correlation of levels of expression with prognostic factor. Moreover, we reported the direct implication of E2F1 in tumorigenicity using transgenic animal models. Recent results from The Cancer Genome Atlas Research Network confirms the presence in human glioblastomas of the genetic alterations in the Rb tumor suppressor pathway, supporting previous reports describing high E2F1 activity in gliomas. In this chapter, we describe methodology to examine the presence of high expression and activity of E2F1, and a practical approach to examine the targeting of this major transcription factor.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Alonso MM, Cascallo M, Gomez-Manzano C, Jiang H, Bekele BN, Perez-Gimenez A, Lang FF, Piao Y, Alemany R, Fueyo J (2007) ICOVIR-5 shows E2F1 addiction and potent antiglioma effect in vivo. Cancer Res 67:8255–8263

    Article  PubMed  CAS  Google Scholar 

  • Alonso MM, Fueyo J, Shay JW, Aldape KD, Jiang H, Lee OH, Johnson DG, Xu J, Kondo Y, Kanzawa T, Kyo S, Bekele BN, Zhou X, Nigro J, McDonald JM, Yung WK, Gomez-Manzano C (2005) Expression of transcription factor E2F1 and telomerase in glioblastomas: mechanistic linkage and prognostic significance. J Natl Cancer Inst 97:1589–1600

    Article  PubMed  CAS  Google Scholar 

  • Bandara LR, La Thangue NB (1991) Adenovirus E1a prevents the retinoblastoma gene product from complexing with a cellular transcription factor. Nature 351:494–497

    Article  PubMed  CAS  Google Scholar 

  • Cavenee WK, Dryja TP, Phillips RA, Benedict WF, Godbout R, Gallie BL, Murphree AL, Strong LC, White RL (1983) Expression of recessive alleles by chromosomal mechanisms in retinoblastoma. Nature 305:779–784

    Article  PubMed  CAS  Google Scholar 

  • Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR (1991) The E2F transcription factor is a cellular target for the RB protein. Cell 65:1053–1061

    Article  PubMed  CAS  Google Scholar 

  • Christensen J, Cloos P, Toftegaard U, Klinkenberg D, Bracken AP, Trinh E, Heeran M, Di Stefano L, Helin K (2005) Characterization of E2F8, a novel E2F-like cell-cycle regulated repressor of E2F-activated transcription. Nucleic Acids Res 33:5458–5470

    Article  PubMed  CAS  Google Scholar 

  • Classon M, Harlow E (2002) The retinoblastoma tumour suppressor in development and cancer. Nat Rev Cancer 2:910–917

    Article  PubMed  CAS  Google Scholar 

  • Dyson N (1998) The regulation of E2F by pRB-family proteins. Genes Dev 12:2245–2262

    Article  PubMed  CAS  Google Scholar 

  • Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP (1986) A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 323:643–646

    Article  PubMed  CAS  Google Scholar 

  • Fueyo J, Gomez-Manzano C, Alemany R, Lee PS, McDonnell TJ, Mitlianga P, Shi YX, Levin VA, Yung WK, Kyritsis AP (2000) A mutant oncolytic adenovirus targeting the Rb pathway produces anti-glioma effect in vivo. Oncogene 19:2–12

    Article  PubMed  CAS  Google Scholar 

  • Haller F, Gunawan B, von Heydebreck A, Schwager S, Schulten HJ, Wolf-Salgo J, Langer C, Ramadori G, Sultmann H, Fuzesi L (2005) Prognostic role of E2F1 and members of the CDKN2A network in gastrointestinal stromal tumors. Clin Cancer Res 11:6589–6597

    Article  PubMed  CAS  Google Scholar 

  • Han S, Park K, Bae BN, Kim KH, Kim HJ, Kim YD, Kim HY (2003) E2F1 expression is related with the poor survival of lymph node-positive breast cancer patients treated with fluorouracil, doxorubicin and cyclophosphamide. Breast Cancer Res Treat 82:11–16

    Article  PubMed  CAS  Google Scholar 

  • Harbour JW, Dean DC (2000) The rb/E2F pathway: expanding roles and emerging paradigms. Genes Dev 14:2393–2409

    Article  PubMed  CAS  Google Scholar 

  • Harbour JW, Luo RX, Dei Santi A, Postigo AA, Dean DC (1999) Cdk phosphorylation triggers sequential intramolecular interactions that progressively block Rb functions as cells move through G1. Cell 98:859–869

    Article  PubMed  CAS  Google Scholar 

  • Helin K, Lees JA, Vidal M, Dyson N, Harlow E, Fattaey A (1992) A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell 70:337–350

    Article  PubMed  CAS  Google Scholar 

  • Hernando E, Nahlâe Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M, Michel L, Mittal V, Gerald W, Benezra R, Lowe SW, Cordon-Cardo C (2004) Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature 430:797–802

    Article  PubMed  CAS  Google Scholar 

  • Irwin M, Marin MC, Phillips AC, Seelan RS, Smith DI, Liu W, Flores ER, Tsai KY, Jacks T, Vousden KH, Kaelin WG Jr (2000) Role for the p53 homologue p73 in E2F-1-induced apoptosis. Nature 407:645–648

    Article  PubMed  CAS  Google Scholar 

  • Kaelin WG Jr, Krek W, Sellers WR, DeCaprio JA, Ajchenbaum F, Fuchs CS, Chittenden T, Li Y, Farnham PJ, Blanar MA (1992) Expression cloning of a cDNA encoding a retinoblastoma-binding protein with E2F-like properties. Cell 70:351–364

    Article  PubMed  CAS  Google Scholar 

  • Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823

    Article  PubMed  Google Scholar 

  • Kovesdi I, Reichel R, Nevins JR (1986a) E1A transcription induction: enhanced binding of a factor to upstream promoter sequences. Science 231:719–722

    Article  PubMed  CAS  Google Scholar 

  • Kovesdi I, Reichel R, Nevins JR (1986b) Identification of a cellular transcription factor involved in E1A trans-activation. Cell 45:219–228

    Article  PubMed  CAS  Google Scholar 

  • Kovesdi I, Reichel R, Nevins JR (1987) Role of an adenovirus E2 promoter binding factor in E1A-mediated coordinate gene control. Proc Natl Acad Sci USA 84:2180–2184

    Article  PubMed  CAS  Google Scholar 

  • Kowalik TF, DeGregori J, Leone G, Jakoi L, Nevins JR (1998) E2F1-specific induction of apoptosis and p53 accumulation, which is blocked by mdm2. Cell Growth Diff 9:113–118

    PubMed  CAS  Google Scholar 

  • La Thangue NB (2003) The yin and yang of E2F-1: balancing life and death. Nat Cell Biol 5:587–589

    Article  PubMed  Google Scholar 

  • Lal S, Lacroix M, Tofilon P, Fuller GN, Sawaya R, Lang FF (2000) An implantable guide-screw system for brain tumor studies in small animals. J Neurosurg 92:326–333

    Article  PubMed  CAS  Google Scholar 

  • Leone G, DeGregori J, Yan Z, Jakoi L, Ishida S, Williams RS, Nevins JR (1998) E2F3 activity is regulated during the cell cycle and is required for the induction of S phase. Genes Dev 12:2120–2130

    Article  PubMed  CAS  Google Scholar 

  • Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 25:402–408

    Article  PubMed  CAS  Google Scholar 

  • Lundberg AS, Weinberg RA (1998) Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. Mol Cell Biol 18:753–761

    PubMed  CAS  Google Scholar 

  • Majem M, Cascallo M, Bayo-Puxan N, Mesia R, Germa JR, Alemany R (2006) Control of E1A under an E2F-1 promoter insulated with the myotonic dystrophy locus insulator reduces the toxicity of oncolytic adenovirus ad-Delta24RGD. Cancer Gene Ther 13:696–705

    Article  PubMed  CAS  Google Scholar 

  • Muller H, Bracken AP, Vernell R, Moroni MC, Christians F, Grassilli E, Prosperini E, Vigo E, Oliner JD, Helin K (2001) E2Fs regulate the expression of genes involved in differentiation, development, proliferation, and apoptosis. Genes Dev 15:267–285

    Article  PubMed  CAS  Google Scholar 

  • Nevins JR (1992) E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258:424–429

    Article  PubMed  CAS  Google Scholar 

  • Nevins JR (1998) Toward an understanding of the functional complexity of the E2F and retinoblastoma families. Cell Growth Differ 9:585–593

    PubMed  CAS  Google Scholar 

  • Olson MV, Johnson DG, Jiang H, Xu J, Alonso MM, Aldape KD, Fuller GN, Bekele BN, Yung WK, Gomez-Manzano C, Fueyo J (2007) Transgenic E2F1 expression in the mouse brain induces a human-like bimodal pattern of tumors. Cancer Res 67:4005–4009

    Article  PubMed  CAS  Google Scholar 

  • Parr MJ, Manome Y, Tanaka T, Wen P, Kufe DW, Kaelin WG Jr, Fine HA (1997) Tumor-selective transgene expression in vivo mediated by an E2F-responsive adenoviral vector. Nat Med 3:1145–1149

    Article  PubMed  CAS  Google Scholar 

  • Ren B, Cam H, Takahashi Y, Volkert T, Terragni J, Young RA, Dynlacht BD (2002) E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints. Genes Dev 16:245–256

    Article  PubMed  CAS  Google Scholar 

  • Sardet C, Vidal M, Cobrinik D, Geng Y, Onufryk C, Chen A, Weinberg RA (1995) E2F-4 and E2F-5, two members of the E2F family, are expressed in the early phases of the cell cycle. Proc Natl Acad Sci USA 92:2403–2407

    Article  PubMed  CAS  Google Scholar 

  • Stevaux O, Dyson NJ (2002) A revised picture of the E2F transcriptional network and RB function. Curr Opin Cell Biol 14:684–691

    Article  PubMed  CAS  Google Scholar 

  • Trimarchi JM, Fairchild B, Wen J, Lees JA (2001) The E2F6 transcription factor is a component of the mammalian bmi1-containing polycomb complex. Proc Natl Acad Sci USA 98:1519–1524

    Article  PubMed  CAS  Google Scholar 

  • Trimarchi JM, Lees JA (2002) Sibling rivalry in the E2F family. Nat Rev Mol Cell Biol 3:11–20

    Article  PubMed  CAS  Google Scholar 

  • Ueki K, Ono Y, Henson JW, Efird JT, von Deimling A, Louis DN (1996) CDKN2/p16 or RB alterations occur in the majority of glioblastomas and are inversely correlated. Cancer Res 56:150–153

    PubMed  CAS  Google Scholar 

  • Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359:492–507

    Article  PubMed  CAS  Google Scholar 

  • Won J, Chang S, Oh S, Kim TK (2004) Small-molecule-based identification of dynamic assembly of E2F-pocket protein-histone deacetylase complex for telomerase regulation in human cells. Proc Natl Acad Sci USA 101:11328–11333

    Article  PubMed  CAS  Google Scholar 

  • Yamazaki K, Hasegawa M, Ohoka I, Hanami K, Asoh A, Nagao T, Sugano I, Ishida Y (2005) Increased E2F-1 expression via tumour cell proliferation and decreased apoptosis are correlated with adverse prognosis in patients with squamous cell carcinoma of the oesophagus. J Clin Pathol 58:904–910

    Article  PubMed  CAS  Google Scholar 

  • Zhang SY, Liu SC, Al-Saleem LF, Holloran D, Babb J, Guo X, Klein-Szanto AJ (2000) E2F-1: a proliferative marker of breast neoplasia. Cancer Epidemiol Biomark Prev 9:395–401

    CAS  Google Scholar 

  • Ziebold U, Reza T, Caron A, Lees JA (2001) E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos. Genes Dev 15:386–391

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

We thank Ann Sutton (Department of Scientific Publication, The University of Texas M. D. Anderson Cancer Center, Houston, TX) for editorial assistance. This work was supported by an Institutional Research Grant from M. D. Anderson Cancer Center.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Candelaria Gomez-Manzano .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Alonso, M.M., Fueyo, J., Gomez-Manzano, C. (2011). Malignant Gliomas: Role of E2F1 Transcription Factor. In: Hayat, M. (eds) Tumors of the Central Nervous System, Volume 1. Tumors of the Central Nervous System, vol 1. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-0344-5_10

Download citation

  • DOI: https://doi.org/10.1007/978-94-007-0344-5_10

  • Published:

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-007-0343-8

  • Online ISBN: 978-94-007-0344-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics