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Connection between Proliferation Rate and Temozolomide Sensitivity of Primary Glioblastoma Cell Culture and Expression of YB-1 and LRP/MVP

N. I. Moiseeva1*, O. Yu. Susova1, A. A. Mitrofanov1, D. Yu. Panteleev2, G. V. Pavlova2, N. A. Pustogarov2, A. A. Stavrovskaya1, and E. Yu. Rybalkina1*

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

2Institute of Gene Biology, Russian Academy of Sciences, 119334 Moscow, Russia; E-mail: N.I.Moiseeva@gmail.com, Kate_Rybalkina@mail.ru

* To whom correspondence should be addressed.

Received December 31, 2015; Revision received March 18, 2016
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.
KEY WORDS: glioblastoma, primary cell culture, temozolomide, drug resistance, proliferation, YB-1, MVP

DOI: 10.1134/S0006297916060109