Lymphocyte Specific Protein‐1 Suppresses Hepatocarcinogenesis Driven by Mutant β‐catenin and Met Overexpression
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 01, 2019
- Source ID
- 10.1096/fasebj.2019.33.1_supplement.126.11
Entities
People
- Bharat Bhushan
- George Michalopoulos
- John Stoops
- Junyan Tao
- Kelly Koral
- Satdarshan Pal Monga
- Wendy Mars
Organizations
- United States Department of Defense
- University of Pittsburgh