PMID- 23311575
OWN - NLM
STAT- MEDLINE
DCOM- 20130627
LR  - 20151119
IS  - 1362-3095 (Electronic)
IS  - 0955-3002 (Linking)
VI  - 89
IP  - 5
DP  - 2013 May
TI  - Gamma-irradiation induces HER-2/neu overexpression in breast cancer cell lines 
      and sensitivity to treatment with trastuzumab.
PG  - 319-25
LID - 10.3109/09553002.2013.765617 [doi]
AB  - PURPOSE: Overexpression of human epidermal growth factor receptor-2 (HER-2/neu) 
      in breast cancer patients is a prerequisite for treatment with trastuzumab. In 
      the present study, we demonstrate by fluorescence in situ hybridization (FISH) 
      analysis that HER-2/neu gene amplification and chromosome 17 (CEP17) polysomy can 
      be induced by irradiation in human breast cancer cell lines with low basal level 
      of HER-2/neu. MATERIALS AND METHODS: The irradiation-induced HER-2/neu gene 
      amplification and CEP17 polysomy enhanced HER-2/neu at the protein level in both 
      human MDA-MB-231 and MDA-MB-435 breast cancer cell lines which was determined by 
      immunohistochemistry and fluorescence analysis and was correlated with mRNA 
      levels. RESULTS: Irradiation affected to a high degree the responsiveness of both 
      cell lines to in vitro treatment with trastuzumab. The direct antiproliferative 
      effect of trastuzumab, as well as its capacity to induce natural killer (NK) 
      cell-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), was 
      considerably higher in the irradiated tumor cells compared to their 
      non-irradiated counterparts. CONCLUSION: Our data demonstrate that irradiation 
      induces HER-2/neu gene amplification and CEP17 polysomy thereby enhancing 
      expression of this protein in breast cancer cell lines rendering them susceptible 
      to treatment with trastuzumab. They also suggest that patients with HER-2/neu 
      negative inoperable tumors undergoing local radiation therapy may benefit from 
      treatment with trastuzumab.
FAU - Voutsas, Ioannis F
AU  - Voutsas IF
AD  - Cancer Immunology and Immunotherapy Center, Saint Savas Cancer Hospital, Athens, 
      Greece.
FAU - Mahaira, Louisa G
AU  - Mahaira LG
FAU - Fotopoulou, Katerina
AU  - Fotopoulou K
FAU - Kapranos, Nikiforos
AU  - Kapranos N
FAU - Reclos, John G
AU  - Reclos JG
FAU - Gritzapis, Angelos D
AU  - Gritzapis AD
FAU - Papamichail, Michail
AU  - Papamichail M
FAU - Perez, Sonia A
AU  - Perez SA
FAU - Baxevanis, Constantin N
AU  - Baxevanis CN
LA  - eng
PT  - Journal Article
DEP - 20130201
PL  - England
TA  - Int J Radiat Biol
JT  - International journal of radiation biology
JID - 8809243
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*pharmacology/therapeutic use
MH  - Breast Neoplasms/*pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects/radiation effects
MH  - Chromosome Aberrations/drug effects/radiation effects
MH  - Chromosomes, Human, Pair 17/drug effects/genetics/radiation effects
MH  - Combined Modality Therapy/*methods
MH  - Drug Resistance, Neoplasm/radiation effects
MH  - Gamma Rays/*therapeutic use
MH  - Gene Expression Regulation, Neoplastic/*drug effects/*radiation effects
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Receptor, ErbB-2/*metabolism
MH  - Trastuzumab
EDAT- 2013/01/15 06:00
MHDA- 2013/06/29 06:00
CRDT- 2013/01/15 06:00
PHST- 2013/01/15 06:00 [entrez]
PHST- 2013/01/15 06:00 [pubmed]
PHST- 2013/06/29 06:00 [medline]
AID - 10.3109/09553002.2013.765617 [doi]
PST - ppublish
SO  - Int J Radiat Biol. 2013 May;89(5):319-25. doi: 10.3109/09553002.2013.765617. Epub 
      2013 Feb 1.