Identification of
            <i>Notch1</i>
            as a Frequent Target for Provirus Insertional Mutagenesis in T-Cell Lymphomas Induced by Leukemogenic Mutants of Mouse Mammary Tumor Virus

Yanagawa, Shin-ichi; Lee, Jong-Seo; Kakimi, Kazuhiro; Matsuda, Yukihiro; Honjo, Tasuku; Ishimoto, Akinori

doi:10.1128/jvi.74.20.9786-9791.2000

Cited by 31 publications

(23 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ICN associates with transcriptional factors, regulating the expression of target genes and modulating the development and growth of cells. 16,17 To date, 4 vertebrate Notch genes have been identified: Notch-1-4. In addition, 4 ligands, such as Dll-1, Dll-4, Jagged-1 and Jagged-2, have also been identified in vertebrates.…”

mentioning

confidence: 99%

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

Wang

Zhang

Banerjee

et al. 2005

Intl Journal of Cancer

120

View full text Add to dashboard Cite

This article has been retracted at the request of: Editor‐in‐Chief and Author ‘Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells’, by Wang, Z., Zhang, Y., Banerjee, S., Li, Y. and Sarkar, F. H. The above article and associated erratum, published online on 11 November 2005 and 6 February 2014, respectively, in Wiley Online Library (http://wileyonlinelibrary.com), have been retracted by agreement between the authors, the journal Editor‐in‐Chief, Professor Peter Lichter, and Wiley Periodicals, Inc. In addition to what was corrected in the erratum, a university investigation involving the first and the corresponding author determined that several figures in this paper were re‐used, mislabeled, manipulated, or duplicated while processing/compiling the final figures assembled from the original data sources. Therefore, the authors are retracting the paper in its entirety although they maintain that these issues did not affect the major conclusions. They apologize for any inconvenience this may have caused. Reference Wang, Z., Zhang, Y., Banerjee, S., Li, Y. and Sarkar, F. H. (2006), Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells. Int. J. Cancer, 118:1930–1936. doi:10.1002/ijc.21589; corrected by Erratum: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells. Int. J. Cancer, 134: E3. doi: .

show abstract

mentioning

confidence: 99%

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

Wang

Zhang

Banerjee

et al. 2005

Intl Journal of Cancer

120

View full text Add to dashboard Cite

show abstract

“…NICD translocates to the nucleus and associates with transcription factors, modulating the gene expression of target genes and the development and growth of cells. 24 27 indicating that Notch signaling could be a factor for the pathogenesis of ITP. Therefore, the imbalance of Th17/Treg may be because of the aberrant expression of Notch signaling in ITP.…”

mentioning

confidence: 99%

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Liu

et al. 2015

Laboratory Investigation

View full text Add to dashboard Cite

T helper 17 (Th17) cells and regulatory T (Treg) cells, along with Th1 and Th2 cells, may contribute to the development of immune thrombocytopenia (ITP). The imbalance of Th17/Treg toward Th17 cells has been shown to play a pivotal role in the peripheral immune response. Notch signaling has been implicated in peripheral T-cell activation and effector cell differentiation. However, the role of Th17/Treg in the pathogenesis of ITP and the effect of Notch signaling on Th17/Treg imbalances remain largely elusive in ITP. In vitro, we treated peripheral blood mononuclear cells (PBMCs) from ITP and healthy controls with g-secretase inhibitor (DAPT). Th17 cells and Treg cells were measured by flow cytometry and IL-17, IL-21, and IL-10 secretion by enzyme immunoassay technique. The mRNA expression of Ntoch1, Hes1, Hey1, RORgt, and Foxp3 was investigated by RT-PCR. Cell proliferation and apoptosis were determined by the Cell Counting Kit-8 and apoptosis detection kit. We demonstrated that DAPT was effective in inhibiting mRNA expression of Notch signaling molecules. In untreated cultured PBMCs from ITP patients, we observed elevated Th17 cell and IL-21 levels and RORgt mRNA expression, decreased Treg cells and Foxp3 mRNA expression, and an increased ratio of Th17/Treg and RORgt/Foxp3. After inactivating Notch signal by DAPT, Th17 cells and Th17/Treg ratio were dose dependently decreased and accompanied by the reduction of IL-17 in culture supernatants and RORgt mRNA expression in ITP patients. However, no significant difference was found for Treg cells and Foxp3 mRNA expression, RORgt/Foxp3 ratio, and IL-21 and IL-10 levels after DAPT treatment in ITP patients. We also present evidence that the effect of DAPT inhibition on the Th17 cell response was associated with downregulation of RORgt and IL-17 transcription using human in vitro polarization. In conclusion, our findings highlight the importance of Notch signaling in Th17/Treg imbalances in ITP. Inactivation of Notch signaling might be a potential immunoregulatory strategy in ITP patients.

show abstract

“…Retroviral insertional mutagenesis (RIM) in mice is a robust strategy that has been used to identify genes that are involved in human leukemia, including Ikzf1 (Ikaros), Notch1, and Lmo2 in T-ALL (29)(30)(31)(32). We used the MOL4070LTR retrovirus (33) to perform RIM in Mx1-Cre, Kras G12D mice.…”

mentioning

confidence: 99%

Mutant Ikzf1, Kras ^G12D , and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents

Dail¹,

Li²,

McDaniel³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Mice that accurately model the genetic diversity found in human cancer are valuable tools for interrogating disease mechanisms and investigating novel therapeutic strategies. We performed insertional mutagenesis with the MOL4070LTR retrovirus in Mx1-Cre, Kras G12D mice and generated a large cohort of T lineage acute lymphoblastic leukemias (T-ALLs). Molecular analysis infers that retroviral integration within Ikzf1 is an early event in leukemogenesis that precedes Kras G12D expression and later acquisition of somatic Notch1 mutations. Importantly, biochemical analysis uncovered unexpected heterogeneity, which suggests that Ras signaling networks are remodeled during multistep tumorigenesis. We tested tumor-derived cell lines to identify biomarkers of therapeutic response to targeted inhibitors. Whereas all T-ALLs tested were sensitive to a dual-specificity phosphoinosityl 3-kinase/mammalian target of rapamycin inhibitor, biochemical evidence of Notch1 activation correlated with sensitivity to γ-secretase inhibition. In addition, Kras G12D T-ALLs were more responsive to a MAP/ERK kinase inhibitor in vitro and in vivo. Together, these studies identify a genetic pathway involving Ikzf1, Kras G12D , and Notch1 in T lineage leukemogenesis, reveal unexpected diversity in Ras-regulated signaling networks, and define biomarkers of drug responses that may inform treatment strategies.

show abstract

Identification of Notch1 as a Frequent Target for Provirus Insertional Mutagenesis in T-Cell Lymphomas Induced by Leukemogenic Mutants of Mouse Mammary Tumor Virus

Cited by 31 publications

References 38 publications

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Mutant Ikzf1, Kras ^G12D , and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents

Contact Info

Product

Resources

About

Identification of Notch1 as a Frequent Target for Provirus Insertional Mutagenesis in T-Cell Lymphomas Induced by Leukemogenic Mutants of Mouse Mammary Tumor Virus

Cited by 31 publications

References 38 publications

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

Retracted: Inhibition of nuclear factor κb activity by genistein is mediated via Notch‐1 signaling pathway in pancreatic cancer cells

Inactivation of Notch signaling reverses the Th17/Treg imbalance in cells from patients with immune thrombocytopenia

Mutant Ikzf1, Kras G12D , and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents

Contact Info

Product

Resources

About

Mutant Ikzf1, Kras ^G12D , and Notch1 cooperate in T lineage leukemogenesis and modulate responses to targeted agents