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RESEARCH PRODUCT

Proton-irradiated breast cells: molecular points of view

Valentina Bravatà 1*Francesco Paolo CammarataLuigi Minafra 1** Pietro Pisciotta 12 6 Concetta ScazzoneLorenzo Manti 4Gaetano SavocaGiada Petringa 12Giuseppe A.p. Cirrone 2Giacomo Cuttone 2Maria C. Gilardi 15Giusi I. Forte 1Giorgio Russo 1

subject

breast cancer cDNA microarray gene signature proton therapy radiation Breast Breast Neoplasms Cell Line Tumor DNA Complementary Dose-Response Relationship Radiation Female Gene Expression Profiling Gene Expression Regulation Neoplastic Humans Inflammation MCF-7 Cells Oligonucleotide Array Sequence Analysis Phenotype Proton Therapy Radiation Tolerance Radiotherapy ProtonsDNA ComplementaryHealth Toxicology and Mutagenesismedicine.medical_treatmentBreast NeoplasmsCell fate determinationRadiation Tolerancegene signature03 medical and health sciences0302 clinical medicineBreast cancerbreast cancerCell Line TumorRegular Papermedicineproton therapyHumansRadiology Nuclear Medicine and imagingBreastClonogenic assayBiologyProton therapyOligonucleotide Array Sequence Analysis030304 developmental biologyInflammationcDNA microarray0303 health sciencesRadiotherapyChemistryGene Expression ProfilingBreast cancer; radiation; cDNA microarray; gene signature; proton therapyCancerDose-Response Relationship RadiationGene signaturemedicine.diseaseGene Expression Regulation NeoplasticGene expression profilingRadiation therapyradiationPhenotype030220 oncology & carcinogenesisMCF-7 CellsCancer researchFemaleProtons

description

Abstract Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome

10.1093/jrr/rrz032http://hdl.handle.net/10281/279782