Molecular Medicine

, Volume 17, Issue 11–12, pp 1133–1136 | Cite as

Transcription Factor Networks as Targets for Therapeutic Intervention of Cancer: The Breast Cancer Paradigm

  • Michalis V. Karamouzis
  • Athanasios G. Papavassiliou


It has long been shown that many of the presently used anticancer drugs exert their effects partly through modulating the activity of vital transcription factors. The intricacy of transcriptional regulation still represents the main obstacle for the design of transcription factor-directed agents. Systematic mapping of tumor-specific transcriptional networks and application of new molecular tools have reinforced research interest and efforts in this venue. The case of breast cancer is discussed as a representative example.


  1. 1.
    Singh S, Johnson J, Chellappan S. (2010) Small molecule regulators of Rb-E2F pathway as modulators of transcription. Biochim. Biophys. Acta. 1799:788–94.CrossRefGoogle Scholar
  2. 2.
    Ozcan S, Andrali SS, Cantrell JEL. (2010) Modulation of transcription factor function by O-Glc-NAc modification. Biochim. Biophys. Acta. 1799:353–64.CrossRefGoogle Scholar
  3. 3.
    Battaglia S, Maguire O, Campbell MJ. (2010) Transcription factor co-repressors in cancer biology: roles and targeting. Int. J. Cancer. 126:2511–9.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Pan Y, Tsai CJ, Ma B, Nussinov R. (2010) Mechanisms of transcription factor selectivity. Trends Genet. 26:75–83.CrossRefGoogle Scholar
  5. 5.
    Huang B, Yang XD, Lamb A, Chen LF. (2010) Posttranslational modifications of NF-kappaB: another layer of regulation for NF-kappaB signaling pathway. Cell Signal. 22:1282–90.CrossRefGoogle Scholar
  6. 6.
    Rodriguez-Martinez JA, Peterson-Kaufman KJ, Ansari AZ. (2010) Small-molecule regulators that mimic transcription factors. Biochim. Biophys. Acta. 1799:768–74.CrossRefGoogle Scholar
  7. 7.
    MacQuarrie KL, Fong AP, Morse RH, Tapscott SJ. (2011) Genome-wide transcription factor binding: beyond direct target regulation. Trends Genet. 27:141–8.CrossRefGoogle Scholar
  8. 8.
    Nilsson S, Gustafsson JA. (2011) Estrogen receptors: therapies targeted to receptor subtypes. Clin. Pharmacol. Ther. 89:44–55.CrossRefGoogle Scholar
  9. 9.
    Ahmad N, Kumar R. (2011) Steroid hormone receptors in cancer development: a target for cancer therapeutics. Cancer Lett. 300:1–9.CrossRefGoogle Scholar
  10. 10.
    Karamouzis MV, Konstantinopoulos PA, Papavassiliou AG. (2009) Targeting MET as a strategy to overcome crosstalk-related resistance to EGFR inhibitors. Lancet Oncol. 10:709–17.CrossRefGoogle Scholar
  11. 11.
    Louie MC, McClellan A, Siewit C, Kawabata L. (2010) Estrogen receptor regulates E2F1 expression to mediate tamoxifen resistance. Mol. Cancer Res. 8:343–52.CrossRefGoogle Scholar
  12. 12.
    Zhang Y, et al. (2011) Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes. Breast Cancer Res. 13:R52.CrossRefGoogle Scholar
  13. 13.
    Probst-Hensch NM, et al. (2010) IGFBP2 and IGFBP3 protein expressions in human breast cancer: association with hormonal factors and obesity. Clin. Cancer Res. 16:1025–32.CrossRefGoogle Scholar
  14. 14.
    Carboni JM, et al. (2009) BMS-754807, a small molecule inhibitor of insulin-like growth factor-1R/IR. Mol. Cancer Ther. 8:3341–9.CrossRefGoogle Scholar
  15. 15.
    Chakraborty AK, Welsh A, Digiovanna MP. (2010) Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines. Breast Cancer Res. Treat. 120:327–35.CrossRefGoogle Scholar
  16. 16.
    Aguilera C, et al. (2011) c-Jun N-terminal phosphorylation antagonizes recruitment of the Mbd3/NuRD repressor complex. Nature. 469:231–5.CrossRefGoogle Scholar
  17. 17.
    Zhang X, et al. (2011) Genome-wide analysis reveals PADI4 cooperates with Elk-1 to activate cFos expression in breast cancer cells. PLoS Genet. 7:1–15.Google Scholar
  18. 18.
    Wortham NC, et al. (2009) The DAED box protein p72 regulates ERα-/estrogen-dependent transcription and cell growth, and is associated with improved survival in ERα positive breast cancer. Oncogene. 28:4053–64.CrossRefGoogle Scholar
  19. 19.
    Petrocca F, Lieberman J. (2011) Promise and challenge of RNA interference-based therapy for cancer. J. Clin. Oncol. 29:747–54.CrossRefGoogle Scholar
  20. 20.
    Eades G, et al. (2011) MiR-200a regulates SIRT1 and EMT-like transformation in mammary epithelial cells. J. Biol. Chem. 286:25992–6002.CrossRefGoogle Scholar
  21. 21.
    O’Day E, Lal A. (2010) MicroRNAs and their target gene networks in breast cancer. Breast Cancer Res. 12:201.CrossRefGoogle Scholar
  22. 22.
    Adams BD, Cowee DM, White BA. (2009) The role of miR-206 in the epidermal growth factor (EGF) induced repression of estrogen receptor-α (ERα) signaling and a luminal phenotype in MCF-7 breast cancer cells. Mol. Endocrinol. 23:1215–30.CrossRefGoogle Scholar
  23. 23.
    Somlo G, et al. (2011) Correlation between miRNA and gene expression profiles and response to neoadjuvant chemotherapy in patients with locally advanced and inflammatory breast cancer. J. Clin. Oncol. 29Suppl:A548.CrossRefGoogle Scholar
  24. 24.
    Lai D, Ho KC, Hao Y, Yang X. (2011) Taxol resistance in breast cancer cells is mediated by the Hippo pathway component TAZ and its downstream transcriptional targets Cyr61 and CTGF. Cancer Res. 71:2728–38.CrossRefGoogle Scholar
  25. 25.
    Wu Y, Zhou BP. (2010) TNF-alpha/NF-kappaB/Snail pathway in cancer cell migration and invasion. Br. J. Cancer. 102:639–44.CrossRefGoogle Scholar
  26. 26.
    Hisamatsu Y, et al. (2011) The expression of GATA-3 and FOXA1 in breast cancer: the bio-markers of hormone sensitivity in luminal-type tumors. J. Clin. Oncol. 29Suppl:A599.CrossRefGoogle Scholar
  27. 27.
    McCune K, et al. (2010) Prognosis of hormone-dependent breast cancers: implications of the presence of dysfunctional transcriptional networks activated by insulin via the immune transcription factor T-bet. Cancer Res. 70:685–96.CrossRefGoogle Scholar
  28. 28.
    Ring A, Evgrafov O, Knwoles J, Kahn M. (2011) Targeting _-catenin/CBP interaction in breast cancer. J. Clin. Oncol. 29Suppl:A10516.CrossRefGoogle Scholar
  29. 29.
    Kim E, et al. (2011) Biomarkers affecting metastasis and survival in paired tissues of 107 patients with metastatic breast cancer. J. Clin. Oncol. 29Suppl:A10630.CrossRefGoogle Scholar
  30. 30.
    Marzese DM, et al. (2011) The relationship between the number of aberrantly methylated regions and the methylation status of p73 and RARβ genes and prognosis in patients with breast cancer. J. Clin. Oncol. 29Suppl:A10542.CrossRefGoogle Scholar
  31. 31.
    Simpson N, Syed BM, Morgan DAL, Ellis IO, Cheung K. (2011) Pattern of estrogen receptor (ER)/progesterone receptor (PR)/HER2 expression in older women with primary breast cancer based on core needle biopsies and correlation with short-term clinical outcome. J. Clin. Oncol. 29Suppl:Ae21104.CrossRefGoogle Scholar
  32. 32.
    Basik M, et al. (2011) Measurement of Pax2, TC21, CCND1, and RFS1 as predictive biomarkers for outcomes in the NCIC CTG MA.12 trial of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer. J. Clin. Oncol. 29Suppl:A560.CrossRefGoogle Scholar
  33. 33.
    Giordano A, et al. (2011) Epithelial-mesenchymal transition in patients with HER2+ metastatic breast cancer. J. Clin. Oncol. 29Suppl:A623.CrossRefGoogle Scholar
  34. 34.
    Siegel PM, Muller WJ. (2010) Transcription factor regulatory networks in mammary epithelial development and tumorigenesis. Oncogene. 29:2753–9.CrossRefGoogle Scholar
  35. 35.
    Casas E, et al. (2011) Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res. 71:245–54.CrossRefGoogle Scholar
  36. 36.
    Haftchenary S, Avadisian M, Gunning PT. (2011) Inhibiting aberrant Stat3 function with molecular therapeutics: a progress report. Anti-Cancer Drugs. 22:115–27.CrossRefGoogle Scholar
  37. 37.
    Bodily JM, Mehta KP, Laimins LA. (2011) Human papillomavirus E7 enhances hypoxia-inducible factor 1-mediated transcription by inhibiting binding of histone deacetylases. Cancer Res. 71:1187–95.CrossRefGoogle Scholar
  38. 38.
    Yin L, Velazquez OC, Liu ZJ. (2010) Notch signaling: emerging molecular targets for cancer therapy. Biochem. Pharmacol. 80:690–701.CrossRefGoogle Scholar
  39. 39.
    Konstantinopoulos PA, Papavassiliou AG. (2011) Seeing the future of cancer-associated transcription factor drug targets. JAMA. 305:2349–50.CrossRefGoogle Scholar
  40. 40.
    Karamouzis MV, Konstantinopoulos PA, Papavassiliou AG. (2007) Epigenomics in respiratory epithelium carcinogenesis: prevention and therapeutic challenges. Cancer Treat. Rev. 33:284–8.CrossRefGoogle Scholar

Copyright information

© The Feinstein Institute for Medical Research 2011

Authors and Affiliations

  • Michalis V. Karamouzis
    • 1
  • Athanasios G. Papavassiliou
    • 1
  1. 1.Department of Biological Chemistry, Molecular Oncology UnitUniversity of Athens Medical SchoolAthensGreece

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