دورية أكاديمية

Protons sensitize epithelial cells to mesenchymal transition.

التفاصيل البيبلوغرافية
العنوان: Protons sensitize epithelial cells to mesenchymal transition.
المؤلفون: Wang M; Division of Space Life Sciences, Universities Space Research Association, Houston, Texas, United States of America., Hada M, Saha J, Sridharan DM, Pluth JM, Cucinotta FA
المصدر: PloS one [PLoS One] 2012; Vol. 7 (7), pp. e41249. Date of Electronic Publication: 2012 Jul 23.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Proton Therapy*, Epithelial Cells/*cytology , Epithelial Cells/*radiation effects , Epithelial-Mesenchymal Transition/*radiation effects, Cell Line ; Dose-Response Relationship, Radiation ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Epithelial-Mesenchymal Transition/drug effects ; Esophagus/cytology ; Humans ; Phenotype ; Phosphorylation/drug effects ; Phosphorylation/radiation effects ; Signal Transduction/drug effects ; Signal Transduction/radiation effects ; Smad2 Protein/metabolism ; Smad7 Protein/metabolism ; Transforming Growth Factor beta1/pharmacology ; Up-Regulation/drug effects ; Up-Regulation/radiation effects
مستخلص: Proton radiotherapy has gained more favor among oncologists as a treatment option for localized and deep-seated tumors. In addition, protons are a major constituent of the space radiation astronauts receive during space flights. The potential for these exposures to lead to, or enhance cancer risk has not been well studied. Our objective is to study the biological effects of low energy protons on epithelial cells and its propensity to enhance transforming growth factor beta 1 (TGFβ1)-mediated epithelial-mesenchymal transition (EMT), a process occurring during tumor progression and critical for invasion and metastasis. Non-transformed mink lung epithelial cells (Mv1Lu) and hTERT- immortalized human esophageal epithelial cells (EPC) were used in this study. EMT was identified by alterations in cell morphology, EMT-related gene expression changes determined using real-time PCR, and EMT changes in specific cellular markers detected by immunostaining and western blotting. Although TGFβ1 treatment alone is able to induce EMT in both Mv1Lu and EPC cells, low energy protons (5 MeV) at doses as low as 0.1 Gy can enhance TGFβ1 induced EMT. Protons alone can also induce a mild induction of EMT. SD208, a potent TGFβ Receptor 1 (TGFβR1) kinase inhibitor, can efficiently block TGFβ1/Smad signaling and attenuate EMT induction. We suggest a model for EMT after proton irradiation in normal and cancerous tissue based on our results that showed that low and high doses of protons can sensitize normal human epithelial cells to mesenchymal transition, more prominently in the presence of TGFβ1, but also in the absence of TGFβ1.
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المشرفين على المادة: 0 (Smad2 Protein)
0 (Smad7 Protein)
0 (Transforming Growth Factor beta1)
تواريخ الأحداث: Date Created: 20120731 Date Completed: 20121128 Latest Revision: 20231105
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC3402537
DOI: 10.1371/journal.pone.0041249
PMID: 22844446
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0041249