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Lymphocyte Specific Protein‐1 Suppresses Hepatocarcinogenesis Driven by Mutant β‐catenin and Met Overexpression
Author(s) -
Koral Kelly,
Tao Junyan,
Bhushan Bharat,
Stoops John,
Mars Wendy,
Monga Satdarshan Pal,
Michalopoulos George
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.126.11
Subject(s) - hepatocellular carcinoma , mapk/erk pathway , proliferating cell nuclear antigen , cancer research , cyclin d1 , mutant , genetically modified mouse , biology , transgene , phosphorylation , microbiology and biotechnology , cancer , medicine , immunology , gene , immunohistochemistry , cell cycle , genetics
Lymphocyte specific protein‐1 is the gene with the most copy number variations in a cohort of human hepatocellular carcinoma cases. Previous studies have demonstrated that LSP‐1 acts as a suppressor of hepatocellular proliferation in both cancer cell lines and during liver regeneration after partial hepatectomy as well as an inhibitor of migration. Additionally, concurrent Met overexpression and mutant β‐catenin expression has been demonstrated in 9–12.5% of human HCC cases. Therefore, in the present study, we evaluated whether LSP1 expression affects hepatocarcinogenesis driven by mutant β‐catenin (S45Y) and hMet overexpression by utilizing the sleeping beauty transposase system with hydrodynamic tail vein injections in LSP‐1 transgenic (TG) and WT C57/Bl6 mouse models. LSP1 TG mice overexpress LSP1 specifically in hepatocytes using the albumin promoter, alpha‐fetal protein enhancer. LSP1 TG mice displayed very little histological changes as well as decreased MAPK activation in comparison to the C57 WT mice, which exhibited macroscopic tumors, large PCNA positive proliferating nodules and increased ERK phosphorylation at 7 weeks post injection. Our results demonstrate that expression of LSP1 suppresses mutant β‐catenin and Met driven HCC and may represent a novel therapeutic option for this subset of HCC. Support or Funding Information Supported by Department of Defense grant CA160119, the University of Pittsburgh Menten Endowment, and the Cleveland Foundation Morningstar Fund. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .