Expression of chicken ovalbumin upstream promoter-transcription factor II enhances invasiveness of human lung carcinoma cells.
Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) plays an essential role in angiogenesis and development. It is differentially expressed in tumor cell lines, but its role in carcinogenesis is largely unknown. We demonstrate here that noninvasive human lung cancer cells become invasive when COUP-TFII was expressed. The expression of extracellular matrix degrading proteinases, such as matrix metalloproteinase 2 and urokinase-type plasminogen activator, was up-regulated in these cells. This finding was confirmed by transduction of different human lung cancer cell lines with COUP-TFII protein and also by using antisense expression. We observed disorganization of actin filaments and focal adhesion kinase phosphorylation in COUP-TFII-transfected human lung cancer cells in addition to the increase in extracellular metalloproteinase activity. These results suggest that COUP-TFII may be considered as a new target for anticancer therapies.
Navab
Roya
R
Lung Biology Research Programme and Canadian Institutes of Health Research Group in Lung Development, The Hospital for Sick Children, 555 University Avenue, Montreal, Quebec, Canada M5G 1X8.
Gonzalez-Santos
Juana Maria
JM
Johnston
Michael R
MR
Liu
Jiang
J
Brodt
Pnina
P
Tsao
Ming-Sound
MS
Hu
Jim
J
D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins / Q000235:genetics*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D010957:Plasmids; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011987:Receptors, Steroid; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000199:Actins; D051837:COUP Transcription Factor II; D051836:COUP Transcription Factors; D004268:DNA-Binding Proteins; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2; D011505:Protein-Tyrosine Kinases; D011987:Receptors, Steroid; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator; C496050:PTK2 protein, human; C095569:NR2F2 protein, human