title: Overexpression of axin downregulates TCF-4 and inhibits the development of lung cancer.
abstract: BACKGROUND
  T cell factor 4 (TCF-4) mediates a nuclear response to wingless/int (Wnt) signals by interacting with beta-catenin. Axis inhibition protein (axin) is an important negative regulator of the Wnt signaling pathway. Our aims were to examine the relationship between axin and TCF-4 and to explore the effects of axin on the development of lung cancer.
  
  
  METHODS
  Expression levels of axin and TCF-4 were examined in 107 lung cancer specimens by immunohistochemistry. The axin gene was transfected into lung cancer BE1 cells. The expression levels of axin, beta-catenin, and TCF-4 were detected with immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR) experiments. Apoptosis, proliferation, and the invasive ability of lung cancer cells were examined using flow cytometry, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT), and Matrigel invasive assays.
  
  
  RESULTS
  Preserved axin expression correlated negatively with TCF-4 expression (P = .031). Axin expression differed with respect to degree of differentiation (P = .025) and histological tumor type (P = .031). TCF-4 expression differed relative to tumor, node metastasis (TNM) stage (P = .024). BE1 cells transfected with axin (BE1-axin cells) exhibited a significant decrease in TCF-4 expression. The level of apoptosis in BE1-axin cells was significantly increased, while the proliferative and invasive abilities of BE1-axin cells were decreased.
  
  
  CONCLUSIONS
  These results suggest that reduced expression of axin or augmented expression of TCF-4 is associated with the malignant behavior of lung cancers. Overexpression of axin can downregulate expression of TCF-4 and can inhibit the ability of lung cancer cells to proliferate and invade.
authors.affiliation: Department of Pathology, College of Basic Medical Sciences, China Medical University, Shenyang, 110001, China.
authors.forename: Hong-Tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wei
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Lian-He
authors.initials: LH
authors.lastname: Yang
authors.forename: Shun-Dong
authors.initials: SD
authors.lastname: Dai
authors.forename: Yang
authors.initials: Y
authors.lastname: Han
authors.forename: Juan-Han
authors.initials: JH
authors.lastname: Yu
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.forename: En-Hua
authors.initials: EH
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D060466:Axin Protein; D018286:Carcinoma, Giant Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D058118:Transcription Factor 7-Like 2 Protein; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000378:metabolism
chemical_list: D060466:Axin Protein; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; D058118:Transcription Factor 7-Like 2 Protein; D051176:beta Catenin