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Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer

  • Lin Ding
  • Mohamad El Zaatari
  • Juanita L. MerchantEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 908)

Abstract

This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, “humanized” versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model.

Keywords

GEMMs Notch Hedgehog Gastrin INS-GAS gp130 MNU SPEM 

Notes

Acknowledgements

We would like to acknowledge support from NIH Grant P01-DK64041 (to JLM).

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Lin Ding
    • 1
  • Mohamad El Zaatari
    • 2
  • Juanita L. Merchant
    • 1
    Email author
  1. 1.Departments of Internal Medicine and Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA
  2. 2.Departments of Internal Medicine and Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA

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