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Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers.

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  • Additional Information
    • Source:
      Publisher: College of American Pathologists Country of Publication: United States NLM ID: 7607091 Publication Model: Print Cited Medium: Internet ISSN: 1543-2165 (Electronic) Linking ISSN: 00039985 NLM ISO Abbreviation: Arch. Pathol. Lab. Med. Subsets: Core Clinical (AIM); MEDLINE
    • Publication Information:
      Publication: Northfield, Ill. : College of American Pathologists
      Original Publication: Chicago, American Medical Assn.
    • Subject Terms:
    • Abstract:
      Context: The biologic effects of Notch1 and Notch2 vary with cancer types and their potential role(s) in gastric cancers (GCs) remains largely unknown.
      Objectives: This study aimed to address the previously mentioned issue by checking the expression of Notch1, Notch2, and Notch target gene Hes1 in GCs, premalignant gastric lesions, and noncancerous endoscopic gastric mucosa and by inhibiting Notch signal transduction in GC cells.
      Design: The status of Notch1, Notch2, and Hes1 expression in 74 GC surgical specimens, 10 endoscopic samples, and 4 human GC cell lines was evaluated by tissue microarray-based immunohistochemical staining, Western blotting, and reverse transcription-polymerase chain reaction, and the importance of Notch signaling was elucidated by treating 2 GC cell lines with 2 γ-secretase inhibitors.
      Results: Notch1 was undetectable in noncancerous gastric mucosa but was expressed with nuclear translocation in 16.7% (4 of 24) of chronic gastritis, 50.0% (9 of 18) of intestinal metaplasia, 54.2% (26 of 48) of intestinal GC, and 23.1% (6 of 26) of diffuse GC, showing distinct differences of Notch1 detection rates between either intestinal metaplasia and chronic gastritis or intestinal GCs and diffuse GCs (P  =  .03; P  =  .005, respectively). Notch2 nuclear translocation frequencies were 10.0% (1 of 10) in noncancerous endoscopic mucosa, 71.4% (30 of 42) in premalignant lesions, and 97.3% (72 of 74) in GC tissues, demonstrating a correlation of Notch2 expression with both intestinal GC and diffuse GC formation (P < .001). The rates of nuclear-Hes1 labeling were 1 of 10 among noncancerous, 42.9% premalignant, and 81.1% cancer tissues, which were closely correlated with Notch2 (P < .001) rather than Notch1 (P  =  .42) nuclear translocation. Only Notch2 was expressed accompanied with Hes1 nuclear labeling in the 4 GC cell lines established from diffuse GC cases. Inhibition of Notch signaling with γ-secretase inhibitors, L-685,458 and DAPT, prevented Hes1 nuclear translocation but neither suppressed growth nor induced cell death.
      Conclusions: This study demonstrated a close correlation of Notch2 expression with GC formation and the potential link of Notch1 upregulation with intestinal-like phenotypes of gastric lesions. Although inhibition of Notch activity failed to achieve anti-GC effects, the activated Notch signaling may reflect a potential GC risk.
    • Accession Number:
      0 (Basic Helix-Loop-Helix Transcription Factors)
      0 (Homeodomain Proteins)
      0 (NOTCH1 protein, human)
      0 (NOTCH2 protein, human)
      0 (RNA, Messenger)
      0 (Receptor, Notch1)
      0 (Receptor, Notch2)
      0 (Transcription Factor HES-1)
      149348-15-2 (HES1 protein, human)
    • Publication Date:
      Date Created: 20110407 Date Completed: 20110531 Latest Revision: 20161125
    • Publication Date:
      20200827
    • Accession Number:
      10.1043/2009-0665-OA.1
    • Accession Number:
      21466361
  • Citations
    • ABNT:
      SUN, Y. et al. Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers. Archives of pathology & laboratory medicine, [s. l.], v. 135, n. 4, p. 451–458, 2011. DOI 10.1043/2009-0665-OA.1. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=mdc&AN=21466361. Acesso em: 1 out. 2020.
    • AMA:
      Sun Y, Gao X, Liu J, et al. Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers. Archives of pathology & laboratory medicine. 2011;135(4):451-458. doi:10.1043/2009-0665-OA.1
    • APA:
      Sun, Y., Gao, X., Liu, J., Kong, Q.-Y., Wang, X.-W., Chen, X.-Y., Wang, Q., Cheng, Y.-F., Qu, X.-X., & Li, H. (2011). Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers. Archives of Pathology & Laboratory Medicine, 135(4), 451–458. https://doi.org/10.1043/2009-0665-OA.1
    • Chicago/Turabian: Author-Date:
      Sun, Yuan, Xue Gao, Jia Liu, Qing-You Kong, Xiao-Wei Wang, Xiao-Yan Chen, Qian Wang, Yi-Fan Cheng, Xiao-Xia Qu, and Hong Li. 2011. “Differential Notch1 and Notch2 Expression and Frequent Activation of Notch Signaling in Gastric Cancers.” Archives of Pathology & Laboratory Medicine 135 (4): 451–58. doi:10.1043/2009-0665-OA.1.
    • Harvard:
      Sun, Y. et al. (2011) ‘Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers’, Archives of pathology & laboratory medicine, 135(4), pp. 451–458. doi: 10.1043/2009-0665-OA.1.
    • Harvard: Australian:
      Sun, Y, Gao, X, Liu, J, Kong, Q-Y, Wang, X-W, Chen, X-Y, Wang, Q, Cheng, Y-F, Qu, X-X & Li, H 2011, ‘Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers’, Archives of pathology & laboratory medicine, vol. 135, no. 4, pp. 451–458, viewed 1 October 2020, .
    • MLA:
      Sun, Yuan, et al. “Differential Notch1 and Notch2 Expression and Frequent Activation of Notch Signaling in Gastric Cancers.” Archives of Pathology & Laboratory Medicine, vol. 135, no. 4, Apr. 2011, pp. 451–458. EBSCOhost, doi:10.1043/2009-0665-OA.1.
    • Chicago/Turabian: Humanities:
      Sun, Yuan, Xue Gao, Jia Liu, Qing-You Kong, Xiao-Wei Wang, Xiao-Yan Chen, Qian Wang, Yi-Fan Cheng, Xiao-Xia Qu, and Hong Li. “Differential Notch1 and Notch2 Expression and Frequent Activation of Notch Signaling in Gastric Cancers.” Archives of Pathology & Laboratory Medicine 135, no. 4 (April 2011): 451–58. doi:10.1043/2009-0665-OA.1.
    • Vancouver/ICMJE:
      Sun Y, Gao X, Liu J, Kong Q-Y, Wang X-W, Chen X-Y, et al. Differential Notch1 and Notch2 expression and frequent activation of Notch signaling in gastric cancers. Archives of pathology & laboratory medicine [Internet]. 2011 Apr [cited 2020 Oct 1];135(4):451–8. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=mdc&AN=21466361