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Hepatocyte‐specific GOLM1 Knockout Mice and Human Hepatocellular Carcinoma Cell Lines Provide Insights into Potential Roles for the GOLM1 HCC Serum Biomarker
Author(s) -
Arora Gunisha,
Fimmel Claus,
Wright Lorinda,
Bode Barrie
Publication year - 2015
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.29.1_supplement.1000.3
Subject(s) - cancer research , hepatocellular carcinoma , metastasis , biology , hepatocyte , cell culture , pathology , medicine , cancer , in vitro , genetics
Golgi Protein – 73kDa (GP73/GOLM1) is a resident cis‐Golgi Type II membrane protein that is nearly undetectable in normal hepatocytes, but whose expression increases in hepatocellular carcinoma (HCC). Serum GOLM1 levels increase in patients with chronic hepatitis C infection and HCC, yet its biological role in the liver and in HCC pathogenesis remains unclear. Therefore, liver‐specific GOLM1 null mice were created using the Cre‐loxP system, with floxed GOLM1 gene exon 3 and Cre recombinase driven by the albumin promoter. Mouse genotypes were confirmed by PCR analysis. GOLM1 Fl/Fl /Cre(+) animals showed no obvious biological phenotype compared to their Cre(‐) littermates, exhibited normal growth, behaviors, and mated successfully, suggesting that hepatic GOLM1 is not vital for normal physiological function. Examination of GOLM1 expression in 14 human HCC cell lines revealed that GOLM1 is consistently expressed in mesenchymal cells but not in most epithelial cell lines. Cell invasion assays indicated that mesenchymal HCC with high GOLM1 expression were more invasive suggesting a potential role for GOLM1 in metastasis – a role currently being tested by silencing in invasive mesenchymal HCC cells and over‐expression in non‐invasive epithelial HCC cell lines. Collectively the results suggest that the mice will serve as a valuable tool to investigate the role of GOLM1 in HCC development, and that enhanced GOLM1 expression is linked to post‐epithelial‐mesenchymal transition (EMT) cellular behavior like metastasis. Support: NIU College of Liberal Arts and Sciences