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. Trans-fection 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.
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Work supported by funding from the National Institutes of Health grants CA 49062, ES 11804, NIH Resource Center Grant RR 11623 and Environmental Center grant ES 09089.
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Hei, T.K., Zhao, Y., Zhou, H., Ivanov, V. (2011). Mechanism of Radiation Carcinogenesis: Role of the TGFBI Gene and the Inflammatory Signaling Cascade. In: Rhim, J., Kremer, R. (eds) Human Cell Transformation. Advances in Experimental Medicine and Biology, vol 720. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0254-1_13
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