Skip to main content
SpringerLink
Log in

Connection between proliferation rate and temozolomide sensitivity of primary glioblastoma cell culture and expression of YB-1 and LRP/MVP

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Glioblastomas (GBL) are the most common and aggressive brain tumors. They are distinguished by high resistance to radiation and chemotherapy. To find novel approaches for GBL classification, we obtained 16 primary GBL cell cultures and tested them with real-time PCR for mRNA expression of several genes (YB-1, MGMT, MELK, MVP, MDR1, BCRP) involved in controlling cell proliferation and drug resistance. The primary GBL cultures differed in terms of proliferation rate, wherein a group of GBL cell cultures with low proliferation rate demonstrated higher resistance to temozolomide. We found that GBL primary cell cultures characterized by high proliferation rate and lower resistance to temozolomide expressed higher mRNA level of the YB-1 and MDR1 genes, whereas upregulated expression of MVP/LRP mRNA was a marker in the group of GBL with low proliferation rate and high resistance. A moderate correlation between expression of YB-1 and MELK as well as YB-1 and MDR1 was found. In the case of YB-1 and MGMT expression, no correlation was found. A significant negative correlation was revealed between mRNA expression of MVP/LRP and MELK, MDR1, and BCRP. No correlation in expression of YB-1 and MVP/LRP genes was observed. It seems that mRNA expression of YB-1 and MVP/LRP may serve as a marker for GBL cell cultures belonging to distinct groups, each of which is characterized by a unique pattern of gene activity.

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

Similar content being viewed by others

References

  1. Schwartzbaum, J. A., Fisher, J. L., Aldape, K. D., and Wrensch, M. (2006) Epidemiology and molecular pathology of glioma, Nat. Clin. Pract. Neurol., 2, 494–503.

    Article  PubMed  Google Scholar 

  2. Stupp, R., Hegi, M. E., Mason, W. P., Van den Bent, M. J., Taphoornm, M. J., Janzer, R. C., Ludwin, S. K., Allgeierm, A., Fisher, B., Belanger, K., Hau, P., Brandes, A. A., Gijtenbeekm, J., Marosi, C., Vecht, C. J., Mokhtari, K., Wesseling, P., Villa, S., Eisenhauer, E., Gorlia, T., Weller, M., Lacombe, D., Cairncross, J. G., Mirimanoff, R. O., Stupp, R., Hegi, M. E., and Mason, W. P. (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomized phase III study: 5-year analysis of the EORTC-NCIC trial, Lancet Oncol., 10, 459–466.

    Article  CAS  PubMed  Google Scholar 

  3. Villalva, C., Cortes, U., Wager, M., Tourani, J. M., Rivet, P., Marquant, C., Martin, S., Turhan, A. G., and KarayanTapon, L. (2012) O6-Methylguanine-methyltransferase (MGMT) promoter methylation status in glioma stem-like cells is correlated to temozolomide sensitivity under differentiation-promoting conditions, Int. J. Mol. Sci., 13, 69836994.

    Article  Google Scholar 

  4. Parker, N. R., Khong, P., Parkinson, J. F., Howell, V. M., and Wheeler, H. R. (2015) Molecular heterogeneity in glioblastoma: potential clinical implications, Front. Oncol., 5, 1–9.

    Google Scholar 

  5. Stavrovskaya, A. A., and Gens, G. P. (2014) Some new aspects of investigating multi-drug resistance in tumor cells, Uspekhi Mol. Onkol., 1, 5–11.

    Google Scholar 

  6. Spiegl-Kreinecker, S., Buchroithner, J., Elbling, L., Steiner, E., Wurm, G., Bodenteich, A., Fischer, J., Micksche, M., and Berger, W. (2002) Expression and functional activity of the ABC-transporter proteins P-glycoprotein and multidrug-resistance protein 1 in human brain tumor cells and astrocytes, J. Neurooncol., 57, 27–36.

    Article  PubMed  Google Scholar 

  7. Abe, T., Mori, T., Wakabayashi, Y., Nakagawa, M., Cole, S. P., Koike, K., Kuwano, M., and Hori, S. (1998) Expression of multidrug resistance protein gene in patients with glioma after chemotherapy, J. Neurooncol., 40, 11–18.

    Article  CAS  PubMed  Google Scholar 

  8. Calatozzolo, C., Gelati, M., Ciusani, E., Sciacca, F. L., Pollo, B., Cajola, L., Marras, C., Silvani, A., VitellaroZuccarello, L., Croci, D., Boiardi, A., and Salmaggi, A. (2005) Expression of drug resistance proteins Pgp, MRP1, MRP3, MRP5 and GST-pi in human glioma, J. Neurooncol., 74, 113–121.

    CAS  Google Scholar 

  9. Scheffer, G. L., Wijngaard, P. L., Flens, M. J., Izquierdo, M. A., Slovak, M. L., Pinedo, H. M., Meijer, C. J., Clevers, H. C., and Scheper, R. J. (1995) The drug resistance-related protein LRP is the human major vault protein, Nat. Med., 1, 578–582.

    Article  CAS  PubMed  Google Scholar 

  10. Lotsch, D., Steiner, E., Holzmann, K., Spiegl-Kreinecker, S., Pirker, C., Hlavaty, J., Petznek, H., Hegedus, B., Garay, T., Mohr, T., Sommergruber, W., Grusch, M., and Berger, W. (2013) Major vault protein supports glioblastoma survival and migration by upregulating the EGFR/PI3K signaling axis, Oncotarget, 4, 1904–1918.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lu, C., and Shervington, A. (2008) Chemoresistance in gliomas, Mol. Cell. Biochem., 312, 71–80.

    Article  CAS  PubMed  Google Scholar 

  12. Navarro, L., Gil-Benso, R., Megias, J., Munoz-Hidalgo, L., San-Miguel, T., Callaghan, R. C., Gonzalez-Darder, J. M., Lopez-Gines, C., and Cerda-Nicolas, M. J. (2015) Alteration of major vault protein in human glioblastoma and its relation with EGFR and PTEN status, Neuroscience, 25, 243–251.

    Article  Google Scholar 

  13. Eliseeva, I. A., Kim, E. R., Gur’yanov, S. G., Ovchinnikov, L. P., and Lyabin, D. N. (2011) Y-box-binding protein 1 (YB-1) and its functions, Biochemistry (Moscow), 76, 14021433.

    Article  Google Scholar 

  14. Faury, D., Nantel, A., Dunn, S. E., Guiot, M. C., Haque, T., Hauser, P., Garami, M., Bognar, L., Hanzely, Z., Liberski, P. P., Lopez-Aguilar, E., Valera, E. T., Tone, L. G., Carret, A. S., Del Maestro, R. F., Gleave, M., Montes, J. L., Pietsch, T., Albrecht, S., and Jabado, N. (2007) Molecular profiling identifies prognostic subgroups of pediatric glioblastoma and shows increased YB-1 expression in tumors, J. Clin. Oncol., 25, 1196–1208.

    Article  CAS  PubMed  Google Scholar 

  15. Gao, Y., Fotovati, A., Lee, C., Wang, M., Cote, G., Guns, E., Toyota, B., Faury, D., Jabado, N., and Dunn, S. E. (2009) Inhibition of Y-box binding protein-1 slows the growth of glioblastoma multiforme and sensitizes to temozolomide methyltransferase, Mol. Cancer Ther., 8, 32763284.

    Google Scholar 

  16. Nakano, I., Masterman-Smith, M., Saigusa, K., Paucar, A. A., Horvath, S., Shoemaker, L., Watanabe, M., Negro, A., Bajpai, R., Howes, A., Lelievre, V., Waschek, J. A., Lazareff, J. A., Freije, W. A., Liau, L. M., Gilbertson, R. J., Cloughesy, T. F., Geschwind, D. H., Nelson, S. F., Mischel, P. S., Terskikh, A. V., and Kornblum, H. I. (2008) Maternal embryonic leucine zipper kinase is a key regulator of the proliferation of malignant brain tumors, including brain tumor stem cells, J. Neurosci. Res., 86, 48–60.

    CAS  PubMed  Google Scholar 

  17. Joshi, K., Banasavadi-Siddegowda, Y., Mo, X., Kim, S. H., Mao, P., Kig, C., Nardini, D., Sobol, R. W., Chow, L. M., Kornblum, H. I., Waclaw, R., Beullens, M., and Nakano, I. (2013) MELK-dependent FOXM1 phosphorylation is essential for proliferation of glioma stem cells, Stem Cells, 31, 1051–1063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ganguly, R., Hong, C. S., Smith, L. G., Kornblum, H. I., and Nakano, I. (2014) Maternal embryonic leucine zipper kinase: key kinase for stem cell phenotype in glioma and other cancers, Mol. Cancer Ther., 13, 1393–1398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Stein, U., Bergmann, S., Scheffer, G. L., Scheper, R. J., Royer, H. D., Schlag, P. M., and Walther, W. (2005) YB-1 facilitates basal and 5-fluorouracil-inducible expression of the human major vault protein (MVP) gene, Oncogene, 24, 3606–3618.

    Article  CAS  PubMed  Google Scholar 

  20. Oda, Y., Ohishi, Y., Basaki, Y., Kobayashi, H., Hirakawa, T., Wake, N., Ono, M., Nishio, K., Kuwano, M., and Tsuneyoshi, M. (2007) Prognostic implications of the nuclear localization of Y-box-binding protein-1 and CXCR4 expression in ovarian cancer: their correlation with activated Akt, LRP/MVP and P-glycoprotein expression, Cancer Sci., 98, 1020–1026.

    CAS  PubMed  Google Scholar 

  21. Vayman, A. V., Stromskaya, T. P., Rybalkina, E. Yu., Sorokin, A. V., Gur’yanov, S. G., Zabotina, T. N., Mechetner, E. B., Ovchinnikov, L. P., and Stavrovskaya, A. A. (2006) Intracellular localization and content of YB-1 protein in multidrug resistant tumor cells, Biochemistry (Moscow), 71, 146–154.

    Article  Google Scholar 

  22. Kuwano, M., Oda, Y., Izumi, H., Yang, S. J., Uchiumi, T., Iwamoto, Y., Toi, M., Fujii, T., Yamana, H., Kinoshita, H., Kamura, T., Tsuneyoshi, M., Yasumoto, K., and Kohno, K. (2004) The role of nuclear Y-box binding protein 1 as a global marker in drug resistance, Mol. Cancer Ther., 3, 1485–1492.

    CAS  PubMed  Google Scholar 

  23. Stavrovskaya, A. A., and Stromskaya, T. P. (2008) Transport proteins of the ABC family and multidrug resistance of tumor cells, Biochemistry (Moscow), 73, 735–750.

    Article  Google Scholar 

  24. Stavrovskaya, A., Stromskaya, T., Rybalkina, E., Moiseeva, N., Vaiman, A., Guryanov, S., Ovchinnikov, L., and Guens, G. (2012) YB-1 protein and multidrug resistance of tumor cells, Curr. Signal Trans. Ther., 7, 237–246.

    Article  CAS  Google Scholar 

  25. Fotovati, A., Abu-Ali, S., Wang, P. S., Deleyrolle, L. P., Lee, C., Triscott, J., Chen, J. Y., Franciosi, S., Nakamura, Y., Sugita, Y., Uchiumi, T., Kuwano, M., Leavitt, B. R., Singh, S. K., Jury, A., Jones, C., Wakimoto, H., Reynolds, B. A., Pallen, C. J., and Dunn, S. E. (2011) YB-1 bridges neural stem cells and brain tumor-initiating cells via its roles in differentiation and cell growth, Cancer Res., 71, 5569–5578.

    Article  CAS  PubMed  Google Scholar 

  26. Steiner, E., Holzmann, K., Elbling, L., Micksche, M., and Berger, W. (2006) Cellular functions of vaults and their involvement in multidrug resistance, Curr. Drug Targets, 7, 923–934.

    Article  CAS  PubMed  Google Scholar 

  27. Berger, W., Steiner, E., Grusch, M., Elbling, L., and Micksche, M. (2009) Vaults and the major vault protein: novel roles in signal pathway regulation and immunity, Cell. Mol. Life Sci., 66, 43–61.

    Article  CAS  PubMed  Google Scholar 

  28. Lotsch, D., Steiner, E., Holzmann, K., Spiegl-Kreinecker, S., Pirker, C., Hlavaty, J., Petznek, H., Hegedus, B., Garay, T., Mohr, T., Sommergruber, W., Grusch, M., and Berger, W. (2013) Major vault protein supports glioblastoma survival and migration by upregulating the EGFR/PI3K signaling axis, Oncotarget, 11, 1904–1918.

    Article  Google Scholar 

  29. Henriquez-Hernandez, L. A., Moreno, M., Rey, A., Lloret, M., and Lara, P. C. (2012) MVP expression in the prediction of clinical outcome of locally advanced oral squamous cell carcinoma patients treated with radiotherapy, Radiat. Oncol., 7, doi: 10.1186/1748-717X-7-147.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation, 115487, Moscow, Russia

    N. I. Moiseeva, O. Yu. Susova, A. A. Mitrofanov, A. A. Stavrovskaya & E. Yu. Rybalkina

  2. Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia

    D. Yu. Panteleev, G. V. Pavlova & N. A. Pustogarov

Authors
  1. N. I. Moiseeva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. Yu. Susova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. A. Mitrofanov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Yu. Panteleev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. V. Pavlova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. N. A. Pustogarov
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. A. A. Stavrovskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. Yu. Rybalkina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to N. I. Moiseeva or E. Yu. Rybalkina.

Additional information

Original Russian Text © N. I. Moiseeva, O. Yu. Susova, A. A. Mitrofanov, D. Yu. Panteleev, G. V. Pavlova, N. A. Pustogarov, A. A. Stavrovskaya, E. Yu. Rybalkina, 2016, published in Biokhimiya, 2016, Vol. 81, No. 6, pp. 835-843.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moiseeva, N.I., Susova, O.Y., Mitrofanov, A.A. et al. Connection between proliferation rate and temozolomide sensitivity of primary glioblastoma cell culture and expression of YB-1 and LRP/MVP . Biochemistry Moscow 81, 628–635 (2016). https://doi.org/10.1134/S0006297916060109

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297916060109

Key words

Search

Navigation