Kotsarenko K. Effect of some growth factors and cytokines on the expression of the MGMT repair enzyme gene in somatic mammalian cells in vitro

In our experiments it was shown at a protein level that several growth factors and cytokines (LIF, SCF, IL-3, IFN-alfa2b, EMAP II) influenced on MGMT gene expression in human cell cultures. Growth factors LIF, SCF and IL-3, which are used to block the stem cell differentiation in vitro, demonstrated the ability to cause a significant reduction of MGMT protein amount in human cell cultures. EMAP II protein was shown to have the regulating effect on MGMT gene expression depending on a concentration of the preparations and the peculiarities of the studied cell lines. Recombinant protein IFN-alfa2b at a wide concentration range caused increasing MGMT protein amount in cells, but the action of this cytokine was dependent on the preparation composition. Transgenic carrot extract, which contained recombinant IFN-alfa2b and many other biologically active substances, and Laferobion caused inhibition of MGMT expression in studied human cells. We have found that a number of studied growth factors, cytokines and their complicated preparations induced the MARP (anti-Methyltransferase Antibody Recognizable Protein or MARP) synthesis. We have performed mass spectrometry and bioinformatical analysis of MARP peptide sequence and it has not been shown that MARP is related to MGMT. In the special biological experiments it was shown that 4BL cells, which expressed only MARP, were more resistant to cytotoxic action of complicated alkylating agents with long alkyl groups comparing to simple alkylating agent nitrosoguanidine that may be the evidence of its possible participating in the repair process of induced lesions.