Akt Downregulates B-Cell Translocation Gene-2 Expression Via Erk1/2 Inhibition for Proliferation of Cancer Cells.

B-cell translocation gene 2 (Btg2) is a tumor suppressor gene that is implicated in many biological processes. Akt is a serine/threonine kinase which was originally discovered as an oncogene. The prognostic value of Akt activation in some types of cancers and its effect on tumor suppressor genes remains to be fully elucidated. In the current research we have investigated the Akt-mediated downregulation of Btg2 that increased cells proliferation and cells survival. Human leukemia HL-60, THP-1 and colon cancer DLD-1 cells were used in this study. Inhibition of Akt with LY294002 significantly increased Btg2 mRNA expression while activation of Akt with insulin decreased Btg2 expression. Contrary to this, treatment of cells with U0126, a MAPK kinase inhibitor, significantly abrogated Btg2 expression. Moreover, LY294002 treatment increased Erk1/2 activation, decreased cells proliferation and cells viability while activation of Akt by insulin led to an increase in cells survival and cells division. Exogenous expression of Btg2 decreased cells proliferation both in the presence and absence of insulin and arrested cells at G1 phase. Akt negatively regulates Btg2 via Erk1/2 inhibition that lead to an increase in cells survival and cells proliferation. This elucidates a new mechanism for Btg2 regulation and Akt mediated tumorgenicity.