Ras-mediated up-regulation of survivin expression in cytokine-dependent murine pro-B lymphocytic cells

The Tohoku Journal of Experimental Medicine
Tetsuharu ShinjyoNobuyuki Takasu

Abstract

Survivin, a member of the inhibitor of apoptosis protein (IAP) family, has been widely studied because of its aberrant expression in human cancer. Survivin has multiple functions, including cell-cycle regulation at mitosis, inhibition of apoptosis and caspase-independent cytoprotection. Clinical studies have shown that survivin is associated with resistance to treatment and its expression is linked to poor prognosis. Recent studies indicated that Ras pathways up-regulate survivin expression in hematopoietic cells. Here we analyzed downstream pathways of Ras in interleukin-3 (IL-3)-dependent Baf-3 murine-derived pro-B lymphocytic cells that express constitutively active Ras mutants, using signaling pathway-specific inhibitors. Both mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3-K) pathways are involved in the induction of survivin. Downstream of PI3-K, the signaling pathway is composed of two kinases, Akt and mammalian target of rapamycin (mTOR) pathways. In the downstream targets of PI3-K, mTOR but not Akt is responsible for survivin expression. Using a counterflow centrifugal elutriator, we observed G2/M phase-dominant survivin expression in Baf-3 cells. Interestingly, constitutively active Ras ...Continue Reading

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Citations

Sep 22, 2009·American Journal of Physiology. Lung Cellular and Molecular Physiology·Meng ZhangYang Jin
Apr 23, 2011·Drug Discovery Today·Jagat R KanwarRupinder K Kanwar
Apr 19, 2012·Preparative Biochemistry & Biotechnology·Jirka GrosseDaniela Grimm
Jul 22, 2020·Stem Cell Reviews and Reports·Neerada Meenakshi WarrierPraveen Kumar

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