Negative correlation of LIV-1 and E-cadherin expression in hepatocellular carcinoma cells

PLoS One. 2013;8(2):e56542. doi: 10.1371/journal.pone.0056542. Epub 2013 Feb 20.

Abstract

LIV-1, a zinc transporter, is a mediator downstream of STAT3 both in zebrafish and mammalian cells, and is involved in epithelial-mesenchymal transition (EMT). Despite LIV-1 participates in cancer growth and metastasis, little is known about the association of LIV-1 with human liver cancer development. Therefore, the expression of LIV-1 mRNA was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) in 4 cultured cell lines (3 carcinoma and 1 normal liver cell lines), and the localization of LIV-1 protein was investigated by immunohistochemistry. Expression of LIV-1 protein was analyzed by Western blot both in 4 cultured cell lines and 120 liver tissues (100 carcinoma and 20 histologically normal tissues), and the relationship between its expression and clinicopathological finding was investigated in 100 hepatocellular carcinoma(HCC) tissues. Then stable siRNA expressing Hep-G2 cells were generated to assess the function of LIV-1 in liver cancer cells. We found that LIV-1 mRNA was more highly expressed in liver cancer cell lines compared to normal liver cell line. Western blot showed the expression of LIV-1 was higher in 61% liver carcinoma tissues than that in normal liver tissues. Down-regulated LIV-1 cells showed significant inhibition of proliferation in vitro and reduction of tumor growth in vivo. Furthermore, E-cadherin expression increased in LIV-1 siRNA expressing Hep-G2. These findings indicated that LIV-1 may induce the EMT in HCC cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Cadherins / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cation Transport Proteins / genetics*
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Cell Transformation, Neoplastic / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Middle Aged
  • Neoplasm Proteins / genetics*
  • RNA, Small Interfering

Substances

  • Cadherins
  • Cation Transport Proteins
  • Neoplasm Proteins
  • RNA, Small Interfering
  • SLC39A6 protein, human

Grants and funding

This work was supported in part by grants from the China Postdoctoral Science Fund (20100470107), China Postdoctoral Science Special Fund (201104750), CSCO Fund (Y-B2011-006) and the Fund of the Ministry of Science and Technology of China (2008ZX10002-018). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.