LIV-1 enhances the aggressive phenotype through the induction of epithelial to mesenchymal transition in human pancreatic carcinoma cells

Jun Unno, Kennichi Satoh, Morihisa Hirota, Atsushi Kanno, Shin Hamada, Hiromichi Ito, Atsushi Masamune, Nobukazu Tsukamoto, Fuyuhiko Motoi, Shinichi Egawa, Michiaki Unno, Akira Horii, Tooru Shimosegawa

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

LIV-1 is a downstream target of STAT3 and is essential for the nuclear localization of Snail, a master regulator of epithelial to mesenchymal transition (EMT). Little is known about the association of LIV-1 with pancreatic carcinoma development, therefore, expression of LIV-1 mRNA was analyzed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in 9 cultured cell lines (8 carcinoma and 1 normal duct cell lines) and 24 pancreatic tissues (12 carcinoma and 12 normal tissues). Localization of this gene product was investigated by immunohistochemistry in 72 pancreatic carcinoma and the relation between its expression and clinicopathological findings was examined. To assess the function of LIV-1 in pancreatic carcinoma cells, stable siRNA expressing Panc-1 cells were generated. Higher expression of LIV-1 mRNA was found in both pancreatic carcinoma cell lines and pancreatic carcinoma tissues compared to normal duct cell line and histologically normal tissues, respectively. Immunohistochemical analysis revealed that LIV-1 expression was frequently found in 76.4% of pancreatic carcinoma tissues and its expression level was associated with tumor size and lymphatic infiltration. Down-regulated LIV-1 cells showed significant inhibition of anchorage-dependent or -independent proliferation and cell motility in vitro and reduction of tumor growth and metastasis in vivo. Furthermore, nuclear expression of Snail was decreased and E-cadherin expression was restored in LIV-1 siRNA expressing pancreatic carcinoma cells. These findings indicate that LIV-1 may be involved in acquisition of the aggressive phenotype of human pancreatic carcinoma cells through the induction of epithelial to mesenchymal transition.

Original languageEnglish
Pages (from-to)813-821
Number of pages9
JournalInternational journal of oncology
Volume35
Issue number4
DOIs
Publication statusPublished - 2009 Oct

Keywords

  • Epithelial to mesenchymal transition
  • LIV-1
  • Pancreatic cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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