title: Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.
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.
authors: Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA.
authors: Lin
authors: L
authors: Ding
authors: Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, 1150 West Medical Center Drive, 6518 MSRB 1, Ann Arbor, MI, 48109-5682, USA.
authors: Mohamad
authors: M
authors: El Zaatari
authors: Departments of Internal Medicine and Molecular and Integrative Physiology, University of Michigan, 109 Zina Pitcher PL, BSRB 2051, Ann Arbor, MI, 48109-2200, USA. Merchanj@med.umich.edu.
authors: Juanita L
authors: JL
authors: Merchant
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D051379:Mice; D009154:Mutation; D015398:Signal Transduction / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D025521:Tumor Suppressor Proteins
keywords: GEMMs; Gastrin; Hedgehog; INS-GAS; MNU; Notch; SPEM; gp130