Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access


The most common histological type of RCC is clear cell carcinoma. Although in 70% of the cases renal cancer is diagnosed at the localized stage, metastases develop in more than a half of the patients after surgical treatment. Resistance of RCC against chemotherapy and radiotherapy is the reason of high mortality rate of patients with metastatic renal cancer. Understanding of molecular mechanisms of tumor formation and growth would allow for the development of new diagnostic and prognostic markers, and new treatment strategies of malignant tumors. In this article we discuss the novel trends in the field of treatment of kidney malignant diseases. In particular, we address the questions of prospects and problems of gene therapy approaches for the treatment of kidney cancer. During the recent years we have investigated the DUSP9 gene. This paper summarizes our own data and the results of other investigations of the properties and functions of DUSP9 gene. We conclude that DUSP9 can be considered as a new biomarker for clear cell carcinoma, as well as the gene for kidney cancer gene therapy.

Full Text

Restricted Access

About the authors

A M Granov

Russian Research Center of Radiology and Modern Surgical Technologies

St.-Petersburg, Russia

E I Yakubovich

Russian Research Center of Radiology and Modern Surgical Technologies

St.-Petersburg, Russia

V I Evtushenko

Russian Research Center of Radiology and Modern Surgical Technologies

St.-Petersburg, Russia


  1. Parkin D., Bray F., Ferlay J., Pisani P. Global cancer statistics // CA Cancer J. Clin.— 2005.— Vol. 55.— P. 74—108.
  2. Negrier S., Escudier B., Lasset C. et al. Recombinant human interleukin-2, recombinant human interferon alfa-2a, or both in metastatic renal-cell carcinoma // Engl. J. Med.— 1998.- Vol. 38.- P. 1272-1278.
  3. Van der Veldt A. A., Haanen J. B., van den Eertwegh A. J. et al. Targeted therapy for renal cell cancer: current perspectives // Discov. Med.-2010.- Vol. 10.- P. 394-405.
  4. Imai E., Isaka Y. Perspectives for gene therapy in renal diseases // Intern. Med.- 2004.- Vol. 43, № 2.- P. 85-96.
  5. Mellon M., Bae K-H., Steding C. et al. Suppression of Renal Cell Carcinoma Growth and Metastasis with Sustained Antiangiogenic Gene Therapy // Hum. Gene Ther.- 2008.- Vol. 19, № 5.- Р. 487-495.
  6. Akbulut T., Park F. Gene therapy to the kidney using viral vectors // Paidiatrike.- 2008.- Vol. 71, № 3.- P. 177-185.
  7. Eulitt P., Park M., Hossein H. et al. Enhancing mda-7/IL-24 therapy in renal carcinoma cells by inhibiting multiple protective signaling pathways using sorafenib and by Ad.5/3 gene delivery // Cancer Biology & Therapy.- 2010.- Vol. 10, № 12.- P. 1289-1304.
  8. Marshall E. Biomedicine: gene therapy on trial // Science.- 2000.- Vol. 288.- P. 951-957.
  9. Wu X., Burgess S. M. Integration target site selection for retroviruses and transposable elements // Cell. Mol. Life Sci.- 2004.- Vol. 61, № 19-20.- P. 2588-2596.
  10. Gao X., Kim K-.S., Liu D. Nonviral Gene Delivery: What We Know and What Is Next // AAPS J.- 2007.- Vol. 9, № 1.- P. 92-104.
  11. Pack D. W., Hoffman A. S., Pun S., Stayton P. S. Design and development of polymers for gene delivery // Nature Rev. Drug Discovery.- 2005.- Vol. 4.- P. 581-589.
  12. Bodles-Brakhop A., Heller R., Draghia-Akli R. Electroporation for the Delivery of DNA-based Vaccines and Immunotherapeutics: Current Clinical Developments // Mol Ther.- 2009.- Vol. 17, № 4.- P. 585-592.
  13. Bunuales M., Duzgunes N., Zalba S. et al. Efficient Gene Delivery by EGF-lipoplexes in vitro and in vivo // Nanomedicine.- 2011.- Vol. 6, № 1.- P. 89-98.
  14. Dobson J. Gene therapy progress and prospects: magnetic nanoparticle-based gene delivery // Gene Therapy.- 2006.- Vol. 13.-P. 283-287.
  15. McBain S. C., Yiu H. H., Dobson J. Magnetic nanoparticles for gene and drug delivery // Int. J. Nanomedicine. - 2008.- Vol. 3, № 2.-P. 169-180.
  16. Xu C., Sun S. Superparamagnetic nanoparticles as targeted probes for diagnostic and therapeutic applications // Dalton Trans.- 2009.- Vol. 7, № 29.- Р. 5583-5591.
  17. Marszall M. P. Application of Magnetic Nanoparticles in Pharmaceutical Sciences // Pharm. Res.- 2011.- Vol. 28, № 3.- P. 480-483.
  18. Evtushenko V. I. Protein-binding matrices: Tool for phenol-free gene cloning and vector assembling // Chapter in Book: Manufacturing of Gene Therapeutics: Methods, Processing, Clinical Trials, Regulation, and Validation / Ed. Subramanian.- N.Y.: Kluwer Academic/Plenum Publishers, 2002.- P. 99-133.
  19. Гранов А. М., Евтушенко В. И. Разработка суперпарамагнитных наночастиц для иммобилизации и направленной доставки ДНК-вакцин в опухоли // Мед. акад. журн.- 2009.- T. 9, № 4.- C. 31-36.
  20. Keyse S. M. Dual-specificity MAP kinase phosphatases (MKPs) and cancer // Cancer Metastasis Rev.- 2008.- Vol. 27, № 2.-P. 253-256.
  21. Haagenson K. K., Wu G. S. Mitogen activated protein kinase phosphatases and cancer // Cancer Biol Ther.- 2010.- Vol. 9, № 5.-P. 337-340.
  22. Farooq A., Zhou M. M. Structure and regulation of MAPK phosphatases // Cell. Signal.- 2004.- Vol. 16.- P. 769-779.
  23. Xu H., Dembski M., Yang Q. et al. Dual Specificity Mitogen-activated Protein (MAP) KinasePhosphatase-4 Plays a Potential Role in Insulin Resistance // J. Bio. Chem.- 2003.- Vol. 278, № 32.- Р. 30187-30192.
  24. Muda M., Boschert U., Smith A. et al. Molecular cloning and functional characterization of a novel mitogen activated protein kinase phosphatase, MKP-4 // J. Biol. Chem.- 1997.- Vol. 272.- P. 5141-5151.
  25. Jeong D.-G., Yoon T.-S., Jung S.-K. et al. Exploring binding sites other than the catalytic core in the crystal structure of the catalytic domain of MKP-4 // Acta Cryst.- 2011.- Vol. D67.- P. 25-31.
  26. Christie G., Williams D., Maclsaac F. et al. The dual-specifity protein phosphatase DUSP9/MKP4 is essential for placental function but not required for normal embryonic development // Molecular and Cell Biology.- 2005.- Vol. 25.- P. 8323-8333.
  27. Emanuelli B., Eberle D., Suzuki R., Kahn C. R. Overexpression of the dual-specificity phosphatase MKP-4/DUSP-9 protects against stress-induced insulin resistance // PNAS.- 2008.- Vol. 105, №. 9.- P. 3545-3550.
  28. Voight B., Scott L., Steinthorsdottir V. et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis // Nat. Genet.- 2010.- Vol. 42.- P. 579-589.
  29. Hsu I. R., Kim S. P., Kabir M., Bergman R. N. Metabolic syndrome, hyperinsulinemia, and cancer // Am. J. Clin. Nutr.- 2007.- Vol. 86, № 3.- P. 867-871.
  30. American Cancer Society (2010, June 18). Experts explore emerging evidence linking diabetes and cancer. ScienceDaily.- URL: from /releases/2010/06/100616090023.htm) (Retrieved June 28, 2011).
  31. Чебуркин Ю. В., Князева Т. Г., Петер Ш. и др. Молекулярный портрет карцином почки человека, полученный на основе экспрессии протеин-тирозин-киназ и тирозин-фосфатаз, контролирующих передачу регуляторных сигналов в клетках // Молекулярная биология.- 2002.- Т. 36, № 3.- С. 480-490.
  32. Гранов А. М., Якубович Е. И., Евтушенко В. И. Множественный параллельный анализ экспрессии генов как инструмент молекулярной диагностики рака почки и предстательной железы // Мед. акад. журн.- 2006.- Т. 6, № 1.- С. 131-138.
  33. Gossage L., Eisen T. Alterations in VHL as potential biomarkers in renal-cell carcinoma // Nature Reviews Clinical Oncology.- 2010.-Vol. 7.- P. 277-288.
  34. Гранов А. М., Якубович Е. И., Лавникевич Д. М., Евтушенко В. И. Гендерные различия в метилировании 5 -фланкирующей области гена DUSP9 у больных со светлоклеточной карциномой почки // Мед. акад. журн.- 2008.- Т. 8, № 3.- С. 71-76.
  35. Якубович Е. И., Лавникевич Д. М., Евтушенко В. И. Изменение статуса метилирования гена DUSP9 у пациентов со светлоклеточной карциномой почки // Вопросы онкологии.- 2011.- Т. 57.- С. 70-71.
  36. Omori S., Hida M., Ishikura K. et al. Expression of mitogen-activated protein kinase family in rat renal development // Kidney Int.- 2000.-Vol. 58.- P. 27-37.
  37. Omori S., Fukuzawa R., Hida M. et. al. Expression of mitogen-activated protein kinases in human renal dysplasia // Kidney Int.- 2002.-Vol. 61.- P. 899-906.
  38. Tian W, Zhang Zh., Cohen D. MAPK signaling and the kidney // Am. J. Physiol. Renal Physiol.- 2000.- Vol. 279.- P. 593-604.
  39. Huang D., Ding Y., Luo W. M. et al. Inhibition of MAPK kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo // Cancer Res.- 2008.- Vol. 68.- P. 81-88.
  40. Liu Y., Lagowski J., Sundholm A. et al. Microtubule disruption and tumor suppression by mitogen-activated protein kinase phosphatase 4 // Cancer Res.- 2007.- Vol. 67.- P. 10711-10719.



Abstract - 111

PDF (Russian) - 1


Article Metrics

Metrics Loading ...




  • There are currently no refbacks.

Copyright (c) 2012 Granov A.M., Yakubovich E.I., Evtushenko V.I.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies