Activation of the MAPK signal cascade components phosphorylation involved in the formation of the G0-positive tumor phenotype

Abstract

Introduction. Among the heterogeneous population of tumor cells, there are so-called dormant and senescent cells located in the G0 phase of the cell cycle. The transition to the G0 phase is a stress response mediated, for example, by treatment with chemotherapeutic drugs. The functioning of such cells is associated with the development of non-response. The aim of the study. G0-positive skin melanoma cells modulation with subsequent assessment of the MARK signal cascade molecules, including the main tumor suppressor p53. Material and methods. Skin melanoma cells were incubated with the cytostatic drug dacarbazine to induce the level of G0-positive cells. Total RNA extracted from cells was used for transcriptome analysis, after which the level of phosphorylation of MARK key molecules was evaluated. By immunocytochemistry (ICC) and real-time PCR (PCR-RT) the activity of tumor suppressor p53 was analyzed. Results. As a result of the G0-positive cells level modulation, the MARK signal cascade is among the signaling pathways with the largest number of genes with altered expression. Significantly increased the number of phosphorylated proteins JNK, p70S6K, MEK, RSK1 and RSK2, as well as protein p53, capable of forming a senescent phenotype of tumor cells. Conclusion. When the level of G0-positive skin melanoma cells is modulated by the cytostatic drug dacarbazine, phosphorylation of the MARK signaling cascade components involved in the formation of the G0-positive tumor phenotype increases.