title: Mechanism of radiation carcinogenesis: role of the TGFBI gene and the inflammatory signaling cascade.
abstract: Using an immortalized human bronchial epithelial cell line, we showed previously that the transforming growth factor beta-induced (TGFBI) gene was consistently downregulated by six- to sevenfold among radiation-induced tumorigenic human cells when compared with controls. Transfection of TGFBI gene into tumor cells resulted in a significant reduction in tumor growth as well as in vitro anchorage independent growth. The observations that TGFBI knock-out animals showed increased spontaneous tumor incidence and chemically induced tumors highlight the suppressive nature of the gene. There is evidence that extranuclear/extracellular targets are important in low-dose radiation response and that the cyclo-oxygenase-2 signaling pathway mediates the process. The involvement of NFκB-dependent cytokines and the resultant inflammatory response works in concert with in modulating radiation-induced bronchial carcinogenesis.
authors: Department of Radiation Oncology, Columbia University Medical Center, New York, NY 10032, USA. tkh1@Columbia.edu
authors: Tom K
authors: TK
authors: Hei
authors: Yongliang
authors: Y
authors: Zhao
authors: Hongning
authors: H
authors: Zhou
authors: Vladimir
authors: V
authors: Ivanov
mesh_terms: D000818:Animals; D002869:Chromosome Aberrations; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000150:complications*; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000502:physiology; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D015398:Signal Transduction / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D000099222:betaIG-H3 Protein
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016326:Extracellular Matrix Proteins; D016328:NF-kappa B; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein