| タイトル | Persistent Phenotypic Responses of Human Mammary Epithelial Cells Induced by Ionizing Radiation |
| 本文（外部サイト） | http://naosite.lb.nagasaki-u.ac.jp/dspace/bitstream/10069/21801/1/acta_53_supl_61.pdf |
| 参考URL | http://hdl.handle.net/10069/21801 |
| 著者（英） | Andarawewa L Kumari; Chou S. William; Costes V. Sylvain; Mary Helen Barcellos- Hoff |
| 発行日 | 2009-03 |
| 刊行物名 | Acta medica Nagasakiensia |
| 巻 | 53 |
| 号 | supl. |
| 開始ページ | 61 |
| 終了ページ | 63 |
| 刊行年月日 | 2009-03 |
| 言語 | eng |
| 内容記述 | Ionizing radiation (IR) is a known human breast carcinogen. Although the mutagenic capacity of IR is widely acknowledged as the basis for its action as a carcinogen, we and others have shown that IR can also induce growth factors and extracellular matrix remodeling. We have shown that irradiating human mammary epithelial cells (HMEC) cultured with that transforming growth factor β1 (TGFβ) can generate a persistent phenotype in daughter cells characterized by spindle cell morphology, increased mesenchymal markers, decreased epithelial markers and increased cellular motility and invasion, which are hallmarks of epithelial to mesenchymal transition (EMT). Neither radiation nor TGFβ alone elicited EMT, although IR increased chronic TGFβ signaling and activity. Gene expression profiling revealed that double-treated cells exhibit a specific 10-gene signature associated with Erk/MAPK signaling. We hypothesized that IR-induced MAPK activation primes nonmalignant HMEC to undergo TGFβ-mediated EMT. Consistent with this, Erk phosphorylation was transiently induced by irradiation and persisted in irradiated cells treated with TGFβ, and inhibition of Erk activation, blocked the EMT phenotype. Preliminary studies suggest that eqi-toxic doses of sparsely and densely ionizing radiation resulted in comparable EMT when cells were cultivated in the presence of TGFβ, Furthermore radiation dose response studies show that this effect has a very low threshold in that a single exposure of 3-200 cGy radiation elicits the ‘same’ phenotypic switch, which is consistent with non-targeted effects. Together, these data show that the interactions between radiation-induced signaling pathways elicit heritable phenotypes that could contribute to radiation carcinogenesis. |
| キーワード | Ionizing radiation; TGFβ; Epithelial to Mesenchymal Transition (EMT) |
| 資料種別 | Departmental Bulletin Paper |
| 著者版フラグ | publisher |
| ISSN | 00016055 |
| URI | https://repository.exst.jaxa.jp/dspace/handle/a-is/613331 |
