title: Lack of radiation dose or quality dependence of epithelial-to-mesenchymal transition (EMT) mediated by transforming growth factor β.
abstract: OBJECTIVE
  Epithelial-to-mesenchymal transition (EMT) is a phenotype that alters cell morphology, disrupts morphogenesis, and increases motility. Our prior studies have shown that the progeny of human mammary epithelial cells (HMECs) irradiated with 2 Gy undergoes transforming growth factor β (TGF-β)-mediated EMT. In this study we determined whether radiation dose or quality affected TGF-β-mediated EMT.
  
  
  METHODS
  HMECs were cultured on tissue culture plastic or in Matrigel (BD Biosciences, San Jose, CA) and exposed to low or high linear energy transfer (LET) and TGF-β (400 pg/mL). Image analysis was used to measure membrane-associated E-cadherin, a marker of functional epithelia, or fibronectin, a product of mesenchymal cells, as a function of radiation dose and quality.
  
  
  RESULTS
  E-cadherin was reduced in TGF-β-treated cells irradiated with low-LET radiation doses between 0.03 and 2 Gy compared with untreated, unirradiated cells or TGF-β treatment alone. The radiation quality dependence of TGF-β-mediated EMT was determined by use of 1 GeV/amu (gigaelectron volt/atomic mass unit) (56)Fe ion particles at the National Aeronautics and Space Administration's Space Radiation Laboratory. On the basis of the relative biological effectiveness of 2 for (56)Fe ion particles' clonogenic survival, TGF-β-treated HMECs were irradiated with equitoxic 1-Gy (56)Fe ion or 2-Gy (137)Cs radiation in monolayer. Furthermore, TGF-β-treated HMECs irradiated with either high- or low-LET radiation exhibited similar loss of E-cadherin and gain of fibronectin and resulted in similar large, poorly organized colonies when embedded in Matrigel. Moreover, the progeny of HMECs exposed to different fluences of (56)Fe ion underwent TGF-β-mediated EMT even when only one-third of the cells were directly traversed by the particle.
  
  
  CONCLUSIONS
  Thus TGF-β-mediated EMT, like other non-targeted radiation effects, is neither radiation dose nor quality dependent at the doses examined.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
authors.forename: Kumari L
authors.initials: KL
authors.lastname: Andarawewa
authors.forename: Sylvain V
authors.initials: SV
authors.lastname: Costes
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernandez-Garcia
authors.forename: William S
authors.initials: WS
authors.lastname: Chou
authors.forename: Shraddha A
authors.initials: SA
authors.lastname: Ravani
authors.forename: Howard
authors.initials: H
authors.lastname: Park
authors.forename: Mary Helen
authors.initials: MH
authors.lastname: Barcellos-Hoff
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001940:Breast / Q000166:cytology; D015820:Cadherins / Q000032:analysis*; D018929:Cell Culture Techniques / Q000379:methods; D002588:Cesium Radioisotopes / Q000494:pharmacology; D003094:Collagen; D003114:Colony-Forming Units Assay / Q000379:methods; D004307:Dose-Response Relationship, Radiation; D004338:Drug Combinations; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D005260:Female; D005353:Fibronectins / Q000032:analysis*; D006801:Humans; D007501:Iron / Q000494:pharmacology; D007797:Laminin; D018499:Linear Energy Transfer / Q000502:physiology; D011509:Proteoglycans; D012062:Relative Biological Effectiveness; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D015820:Cadherins; D002588:Cesium Radioisotopes; D004338:Drug Combinations; D005353:Fibronectins; D007797:Laminin; D011509:Proteoglycans; D016212:Transforming Growth Factor beta; C059485:matrigel; D003094:Collagen; D007501:Iron