RRC ID 34560
Author Hayashi Y, Osanai M, Lee GH.
Title NOTCH2 signaling confers immature morphology and aggressiveness in human hepatocellular carcinoma cells.
Journal Oncol Rep
Abstract The NOTCH family of membranous receptors plays key roles during development and carcinogenesis. Since NOTCH2, yet not NOTCH1 has been shown essential for murine hepatogenesis, NOTCH2 rather than NOTCH1 may be more relevant to human hepatocarcinogenesis; however, no previous studies have supported this hypothesis. We therefore assessed the role of NOTCH2 in human hepatocellular carcinoma (HCC) by immunohistochemistry and cell culture. Immunohistochemically, 19% of primary HCCs showed nuclear staining for NOTCH2, indicating activated NOTCH2 signaling. NOTCH2-positive HCCs were on average in more advanced clinical stages, and exhibited more immature cellular morphology, i.e. higher nuclear-cytoplasmic ratios and nuclear densities. Such features were not evident in NOTCH1‑positive HCCs. In human HCC cell lines, abundant NOTCH2 expression was associated with anaplasia, represented by loss of E-cadherin. When NOTCH2 signaling was stably downregulated in HLF cells, an anaplastic HCC cell line, the cells were attenuated in potential for in vitro invasiveness and migration, as well as in vivo tumorigenicity accompanied by histological maturation. Generally, inverse results were obtained for a differentiated HCC cell line, Huh7, manipulated to overexpress activated NOTCH2. These findings suggested that the NOTCH2 signaling may confer aggressive behavior and immature morphology in human HCC cells.
Volume 34(4)
Pages 1650-8
Published 2015-10-1
DOI 10.3892/or.2015.4171
PMID 26252838
PMC PMC4564075
MeSH Anaplasia / genetics Anaplasia / pathology Animals Carcinogenesis / genetics* Carcinoma, Hepatocellular / genetics* Carcinoma, Hepatocellular / pathology Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Gene Expression Regulation, Neoplastic Humans Liver Neoplasms / genetics* Liver Neoplasms / pathology Mice Neoplasm Invasiveness / genetics Neoplasm Invasiveness / pathology Receptor, Notch1 / biosynthesis Receptor, Notch1 / genetics Receptor, Notch2 / biosynthesis* Receptor, Notch2 / genetics Signal Transduction
IF 3.041
Times Cited 10
DNA material pEF-BOSneoSE-mNotch2 RAMIC (RDB06772)