Overexpression of Betaig-h3 gene downregulates integrin alpha5beta1 and suppresses tumorigenicity in radiation-induced tumorigenic human bronchial epithelial cells.
Interaction between cell and extracellular matrix plays a crucial role in tumour invasion and metastasis. Using an immortalised human bronchial epithelial (BEP2D) cell model, the study here shows that expression of Betaig-h3 gene, which encodes a secreted adhesion molecule induced by transforming growth factor-beta, is markedly decreased in several independently generated, radiation-induced tumour cell lines (TL1-TL5) relative to parental BEP2D cells. Transfection of Betaig-h3 gene into tumour cells resulted in a significant reduction in tumour growth. While integrin receptor alpha5beta1 was overexpressed in tumour cells, its expression was corrected to the level found in control BEP2D cells after Betaig-h3 transfection. These data suggest that Betaig-h3 gene is involved in tumour progression by regulating integrin receptor alpha5beta1. The findings provide strong evidence that the Betaig-h3 gene has tumour suppressor function in human BEP2D cell model and suggest a potential target for interventional therapy.
Zhao
Y L
YL
Center for Radiological Research, College of Physicians and Surgeons of Columbia University, VC 11-218, 630 West 168th Street, New York, NY 10032, USA.
Piao
C Q
CQ
Hei
T K
TK
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D015536:Down-Regulation; D004847:Epithelial Cells / Q000528:radiation effects*; D016326:Extracellular Matrix Proteins; D015870:Gene Expression / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017469:Receptors, Fibronectin / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
D017931:DNA Primers; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D017469:Receptors, Fibronectin; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein