title: Differential response of normal and transformed mammary epithelial cells to combined treatment of anti-miR-21 and radiation.
abstract: MicroRNA miR-21 has emerged as a therapeutic target in the treatment of breast cancer. This study was designed to compare the responses of breast cancer cells and non-transformed breast epithelial cells to a combined regimen of miR-21 inhibition and radiation.
  
  
  
  The MDA-MB-361 (breast cancer) and MCF-10A (non-transformed mammary epithelial) cell lines were used for the comparison in this in vitro study. The stable knockdown of miR-21 was performed by using lentiviral approach. The response of the cells was monitored 4, 24 and 48 h after the irradiation with 0.25 and 2.5 Gy, using sham-irradiated cells as controls. The response of the cells was established by performing various functional assays - cell viability and cell attachment, clonogenic survival, cell cycle analysis and 3D microtissue formation.
  
  
  
  The knockdown of miR-21 induced significant increase in apoptosis and growth delay in MDA-MB-361 cancer cells compared to non-transformed MCF-10A cells. After combined radiation and anti-miR-21 treatment, MDA-MB-361 cells show reduced cell growth and viability what is presented in their inability to form colonies. MCF-10A cells were not as sensitive to the combined treatment and that has also been confirmed with colony forming assay.
  
  
  
  Cellular response to a combined treatment of anti-miR-21 and radiation is different between cancer and non-cancer cells which highly support the idea of linking miR-21 inhibitor and radiation treatment in the future therapeutic approaches for breast cancer.
authors.affiliation: a Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Vanja
authors.initials: V
authors.lastname: Radulovic
authors.affiliation: a Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Theresa
authors.initials: T
authors.lastname: Heider
authors.affiliation: a Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Richter
authors.affiliation: a Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Moertl
authors.affiliation: a Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health , Neuherberg , Germany.|b Chair of Radiation Biology , Technical University of Munich , Munich , Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.affiliation: a Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health , Neuherberg , Germany.
authors.forename: Nataša
authors.initials: N
authors.lastname: Anastasov
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D003131:Combined Modality Therapy; D004847:Epithelial Cells / Q000502:physiology / Q000528:radiation effects*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D011878:Radiotherapy / Q000379:methods*; D011879:Radiotherapy Dosage
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs
keywords: Cellular response; MCF-10A; miR-21; radiation oncology