دورية أكاديمية
Heavy ions can enhance TGFβ mediated epithelial to mesenchymal transition.
| العنوان: | Heavy ions can enhance TGFβ mediated epithelial to mesenchymal transition. |
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| المؤلفون: | Wang M; USRA, Division of Life Sciences, Houston, TX 77058, USA., Hada M, Huff J, Pluth JM, Anderson J, O'Neill P, Cucinotta FA |
| المصدر: | Journal of radiation research [J Radiat Res] 2012; Vol. 53 (1), pp. 51-7. |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 0376611 Publication Model: Print Cited Medium: Internet ISSN: 1349-9157 (Electronic) Linking ISSN: 04493060 NLM ISO Abbreviation: J Radiat Res Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: July 2012- : Oxford : Oxford University Press Original Publication: Tokyo : Japan Radiation Research Society |
| مواضيع طبية MeSH: | Iron* , Silicon*, Epithelial Cells/*radiation effects , Epithelial-Mesenchymal Transition/*radiation effects , Heavy Ions/*adverse effects , Transforming Growth Factor beta1/*pharmacology, Animals ; Cell Line, Transformed/drug effects ; Cell Line, Transformed/radiation effects ; Dose-Response Relationship, Radiation ; Epithelial Cells/drug effects ; Epithelial-Mesenchymal Transition/drug effects ; Esophagus/cytology ; Extracellular Matrix Proteins/metabolism ; Humans ; Lung/cytology ; Mink ; Phosphorylation/drug effects ; Protein Processing, Post-Translational/drug effects ; Protein Serine-Threonine Kinases/antagonists & inhibitors ; Pteridines/pharmacology ; Receptor, Transforming Growth Factor-beta Type I ; Receptors, Transforming Growth Factor beta/antagonists & inhibitors ; Recombinant Proteins/pharmacology ; Smad2 Protein/metabolism ; Smad7 Protein/metabolism ; beta Catenin/metabolism |
| مستخلص: | TGFβ is a key modulator of the Epithelial-Mesenchymal Transition (EMT), a process important in cancer progression and metastasis, which leads to the suppression of epithelial genes and expression of mesenchymal proteins. Ionizing radiation was found to specifically induce expression of the TGF-β1 isoform, which can modulate late post-radiation changes and increase the risk of tumor development and metastasis. Interactions between TGFβ induced EMT and DNA damage responses have not been fully elucidated, particularly at low doses and following different radiation quality exposures. Further characterization of the relationship between radiation quality, EMT and cancer development is warranted. We investigated whether space radiation induced TGFβ dependent EMT, using hTERT immortalized human esophageal epithelial cells (EPC2-hTERT) and non-transformed mink lung epithelial cells (Mv1Lu). We have observed morphologic and molecular alterations in EPC2 and Mv1Lu cells consistent with EMT after pre-treatment with TGFβ1. This effect could be efficiently inhibited in both cell lines by the use of a TGFβRI inhibitor. High-energy silicon or iron nuclei were each able to cause a mild induction of EMT, with the inclusion of TGFβ1 inducing a greatly enhanced EMT phenotype even when cells were irradiated with doses as low as 0.1 Gy. A further enhancement of EMT was achieved at a higher dose of 2 Gy. TGFβRI inhibitor was able to reverse the EMT induced by the combination of TGFβ1 and radiation. These studies indicate that heavy ions, even at a low dose, may trigger the process of TGFβ1-induced EMT, and suggest further studies are needed to determine whether the chronic exposures received in space may potentiate this process in astronauts, leading to an increased risk of cancer. |
| معلومات مُعتمدة: | MC_PC_12001 United Kingdom MRC_ Medical Research Council |
| المشرفين على المادة: | 0 (Extracellular Matrix Proteins) 0 (Pteridines) 0 (Receptors, Transforming Growth Factor beta) 0 (Recombinant Proteins) 0 (SD-208) 0 (Smad2 Protein) 0 (Smad7 Protein) 0 (TGFB1 protein, human) 0 (Transforming Growth Factor beta1) 0 (beta Catenin) E1UOL152H7 (Iron) EC 2.7.11.1 (Protein Serine-Threonine Kinases) EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I) Z4152N8IUI (Silicon) |
| تواريخ الأحداث: | Date Created: 20120204 Date Completed: 20120622 Latest Revision: 20211203 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1269/jrr.11121 |
| PMID: | 22302045 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1349-9157 |
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| DOI: | 10.1269/jrr.11121 |