Objectives: 

There were contradictory effects of the proinflammatory cytokine IL6 role in cancer: stimulating tumor growth (leukemia) or inhibiting it (renal neoplasia) and even with variable effects (melanoma), so our objective is to assess the functional role of IL6 in a context of hyperactivation of growth factor-dependent signaling pathways, summing it through the oncogenic Ras (HRasv12) expression.

Materials: 

We established an in vitro model with primary cultured astrocytes obtained from IL6+/+ and IL6-/- mice with three days of life and subsequently transduced by retroviral infection to express HRasv12, recapitulating molecular events commonly altered in human gliomas, such as the overexpression and/or hyperactivation of growth factors signaling pathways. Once we get the study groups of cells: astrocytes IL6+/+, IL6+/+/HRasv12, IL6-/- and IL6-/-/HRasv12, we analyzed their proliferative capacity, senescence and performed morphological and biochemical analysis. The next step is to perform a non-invasive in vivo assay with the injection of these astrocytes in mice brains to monitor the entire tumorigenic process.

Results: 

Our results suggest that presence or absence of IL6 not alters cell proliferation or cell morphology changes induced by oncogenic Ras. Moreover, previous studies showed that this oncogene not induces senescence in astrocytes and we found that the absence of IL6 not changed this peculiarity. The results of immunoblot analysis showed the activation of STAT3, which ensures the activation of the signaling pathway triggered by IL6, and the increase expression level time-dependent, just as happens with p21. p53 levels only vary in groups that express oncogenic Ras due to stress that transformed cells have at DNA level, and the DNA damage response is observed only at the beginning of transformation.

Conclusions: 

The conclusion is that in primary astrocytes cultures IL6 not play an important role in oncogenic Ras-induced processes such as cell proliferation and aggressive morphology acquisition.