scholarly journals MPC-07 MECHANISMS OF BETTER PROGNOSIS IN IDH-MUTATED ASTROCYTOMA WITH 19Q-LOSS

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii23-ii23
Author(s):  
Ryohei Otani ◽  
Takeo Uzuka ◽  
Fumi Higuchi ◽  
Hadzki Matsuda ◽  
Phyo Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Adhesion ◽  
Axon Guidance ◽  
Neuronal Differentiation ◽  
Expression Pattern ◽  
Tumor Immunity ◽  
Cell Shape ◽  
Ras Signaling ◽  
Tumor Proliferation ◽  
Ras Signaling Pathway

Abstract We previously reported that there was a subgroup of IDH-mutated astrocytomas harboring only 19q-loss showing oligodendroglioma-like morphology and significantly longer overall survival (OS) compared with 19q-intact astrocytomas (Otani et al. Cancer Sci 2018). The purpose of the present study was to reveal how 19q-loss contributed to better prognosis and the morphology in the subgroup. We compared expression pattern between five 19q-loss and five 19q-intact IDH-mutated astrocytomas by microarray analysis. 136 up-regulated genes and 203 down regulated genes were extracted in 19q-loss astrocytomas compared with 19q-intact astrocytomas. Significantly changed genes distributed throughout all chromosomes, but more down-regulated genes were on 19q and 4p, and more up-regulated genes were on 4q. Genes associated with apoptosis, cell adhesion, and antigen presentation were up-regulated, and genes associated with Ras signaling pathway were down-regulated. These changes could result in better prognosis. By contrast, there was few expression changed gene associated with oligodendroglioma-like morphology although up-regulation of genes associated with axon guidance and down-regulation of genes associated with cell shape might result in the morphology or neuronal differentiation. Expression pattern of 19q-loss astrocytomas indicated no tendency of oligodendroglial differentiation. Better prognosis of 19q-loss astrocytomas was derived from expression changes associated with tumor proliferation and tumor immunity.

scholarly journals Identification of the functional components of the Ras signaling pathway regulating pituitary cell-specific gene expression.

1994 ◽  
Vol 14 (3) ◽  
pp. 1553-1565 ◽  
Author(s):  
K E Conrad ◽  
J M Oberwetter ◽  
R Vaillancourt ◽  
G L Johnson ◽  
A Gutierrez-Hartmann
Keyword(s):  
Gene Expression ◽  
Pituitary Cell ◽  
Mitogen Activated Protein Kinase ◽  
Specific Gene ◽  
Ras Signaling ◽  
Raf Kinase ◽  
Prolactin Gene ◽  
Ras Signaling Pathway ◽  
Mitogen Activated Protein ◽  
Prolactin Promoter

Ras, a small GTP-binding protein, is required for functional receptor tyrosine kinase signaling. Ultimately, Ras alters the activity of specific nuclear transcription factors and regulates novel patterns of gene expression. Using a rat prolactin promoter construct in transient transfection experiments, we show that both oncogenic Ras and activated forms of Raf-1 kinase selectively stimulated the cellular rat prolactin promoter in GH4 rat pituitary cells. We also show that the Ras signal is completely blocked by an expression vector encoding a dominant-negative Raf kinase. Additionally, using a molecular genetic approach, we determined that inhibitory forms of p42 mitogen-activated protein kinase and an Ets-2 transcription factor interfere with both the Ras and the Raf activation of the rat prolactin promoter. These findings define a functional requirement for these signaling constituents in the activation of the prolactin gene, a cell-specific gene which marks the lactotroph pituitary cell type. Further, this analysis allowed us to order the components in the Ras signaling pathway as it impinges on regulation of prolactin gene transcription as Ras-->Raf kinase-->mitogen-activated protein kinase-->Ets. In contrast, we show that intact c-Jun expression inhibited the Ras-induced activation of the prolactin promoter, defining it as a negative regulator of this pathway, whereas c-Jun was able to enhance the Ras activation of an AP-1-driven promoter in GH4 cells. These data show that c-Jun is not the nuclear mediator of the Ras signal for the highly specialized, pituitary cell-specific prolactin cellular promoter. Thus, we have defined a model system which provides an ideal paradigm for studying Ras/Raf signaling pathways and their effects on neuroendocrine cell-specific gene regulation.

The Ras signaling pathway in Drosophila

1995 ◽  
Vol 5 (1) ◽  
pp. 44-50 ◽  
Author(s):  
David A. Wassarman ◽  
Marc Therrien ◽  
Gerald M. Rubin
Keyword(s):  
Signaling Pathway ◽  
Ras Signaling ◽  
Ras Signaling Pathway

scholarly journals Neural Cell Adhesion Molecule Induces Intracellular Signaling via Multiple Mechanisms of Ca2+ Homeostasis

2006 ◽  
Vol 17 (5) ◽  
pp. 2278-2286 ◽  
Author(s):  
Darya Kiryushko ◽  
Irina Korshunova ◽  
Vladimir Berezin ◽  
Elisabeth Bock
Keyword(s):  
Cell Adhesion ◽  
Neuronal Differentiation ◽  
Adhesion Molecule ◽  
Intracellular Signaling ◽  
Hippocampal Neurons ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Neural Cell ◽  
Src Family Kinases ◽  
Neural Cell Adhesion

The neural cell adhesion molecule (NCAM) plays a pivotal role in the development of the nervous system, promoting neuronal differentiation via homophilic (NCAM–NCAM) as well as heterophilic (NCAM-fibroblast growth factor receptor [FGFR]) interactions. NCAM-induced intracellular signaling has been shown to affect and be dependent on the cytoplasmic Ca2+ concentration ([Ca2+]i). However, the molecular basis of this remains unclear. In this study, we determined [Ca2+]i regulating mechanisms involved in intracellular signaling induced by NCAM. To mimic the effect of homophilic NCAM interaction on [Ca2+]i in vitro, we used a peptide derived from a homophilic binding site of NCAM, termed P2, which triggers signaling cascades similar to those activated by NCAM–NCAM interaction. We found that P2 increased [Ca2+]i in primary hippocampal neurons. This effect depended on two signaling pathways. The first pathway was associated with activation of FGFR, phospholipase Cγ, and production of diacylglycerol, and the second pathway involved Src-family kinases. Moreover, NCAM-mediated Ca2+ entry required activation of nonselective cation and T-type voltage-gated Ca2+ channels. These channels, together with the Src-family kinases, were also involved in neuritogenesis induced by physiological, homophilic NCAM interactions. Thus, unanticipated mechanisms of Ca2+ homeostasis are shown to be activated by NCAM and to contribute to neuronal differentiation.

scholarly journals Post-transcriptional gene regulation by the RNA binding protein IGF2BP3 is critical for MLL-AF4 mediated leukemogenesis

2020 ◽  
Author(s):  
Tiffany M Tran ◽  
Julia Philipp ◽  
Jaspal Bassi ◽  
Neha Nibber ◽  
Jolene Draper ◽  
...  
Keyword(s):  
Rna Binding ◽  
Leukemia Cell ◽  
Cellular Level ◽  
Ras Signaling ◽  
Therapeutic Approaches ◽  
Mrna Targets ◽  
Ras Signaling Pathway ◽  
Stem And Progenitor Cells ◽  
Transcriptional Gene Regulation ◽  
Poor Outcomes

ABSTRACTDespite recent advances in therapeutic approaches, patients with MLL-rearranged leukemia still have poor outcomes and a high risk of relapse. Here, we found that MLL-AF4, the most common MLL fusion protein in patients, transcriptionally induces IGF2BP3 and that IGF2BP3 strongly amplifies MLL-Af4 mediated leukemogenesis. Deletion of Igf2bp3 significantly increases the survival of mice with MLL-Af4 driven leukemia and greatly attenuates disease. At the cellular level, MLL-Af4 leukemia-initiating cells require Igf2bp3 for their function in leukemogenesis. eCLIP and transcriptome analysis of MLL-Af4 transformed stem and progenitor cells and MLL-Af4 bulk leukemia cells reveals a complex IGF2BP3-regulated post-transcriptional operon governing leukemia cell survival and proliferation. Critical mRNA targets include important leukemogenic genes such as in the Hoxa locus and numerous genes within the Ras signaling pathway. Together, our findings show that IGF2BP3 is an essential positive regulator of MLL-AF4 mediated leukemogenesis and is a potential therapeutic target in this disease.

scholarly journals Nogo-B receptor-mediated Ras signaling pathway is a target for suppressing proliferating hemangioma

JCI Insight ◽  
2021 ◽  
Author(s):  
Wenquan Hu ◽  
Zhong Liu ◽  
Valerie Salato ◽  
Paula E. North ◽  
Joyce Bischoff ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ras Signaling ◽  
Ras Signaling Pathway

The effect of aquaporin 5 overexpression on the Ras signaling pathway

2008 ◽  
Vol 367 (2) ◽  
pp. 291-298 ◽  
Author(s):  
Janghee Woo ◽  
Juna Lee ◽  
Myoung Sook Kim ◽  
Se Jin Jang ◽  
David Sidransky ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Ras Signaling ◽  
Aquaporin 5 ◽  
Ras Signaling Pathway
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