Downregulated TIPE2 is associated with poor prognosis and promotes cell proliferation in non-small cell lung cancer

Biochem Biophys Res Commun. 2015 Jan 30;457(1):43-9. doi: 10.1016/j.bbrc.2014.12.080. Epub 2014 Dec 24.

Abstract

The present study aims to investigate the expression pattern of TIPE2 protein and its clinical significance in human non-small cell lung cancer (NSCLC). We investigated the expression levels of TIPE2 in 96 NSCLC tumor samples by immunohistochemistry and then analyzed its clinical significance. Furthermore, the role of TIPE2 on the biological properties of the NSCLC cell line H1299 and A549 was experimentally tested in vitro and in vivo. We found that the expression level of TIPE2 was significantly higher in normal lung tissues compared with NSCLC tissues (P<0.001), and TIPE2 downregulation was significantly correlated with advanced TNM stage (P=0.006). TIPE2 expression was lower in lung cancer cell lines than normal bronchial cell line HBE. Transfection of TIPE2 plasmid was performed in H1299 and A549 cells. TIPE2 overexpression inhibited lung cancer cell proliferation, colony formation and cell invasive in vitro, and prevented lung tumor growth in vivo. In addition, TIPE2 transfection reduced the anti-apoptotic Bcl-XL protein and mesenchymal marker N-cadherin expression. Taken together, our results demonstrate that TIPE2 might serve as a tumor suppressor in NSCLC progression.

Keywords: Invasive; Non-small cell lung cancer; Proliferation; TIPE2; Tumor suppressor.

MeSH terms

  • Animals
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Down-Regulation*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology*
  • Male
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • Tumor Stem Cell Assay
  • Xenograft Model Antitumor Assays
  • bcl-X Protein / metabolism

Substances

  • Cadherins
  • Intracellular Signaling Peptides and Proteins
  • TNFAIP8L2 protein, human
  • bcl-X Protein