Adenovirus-mediated expression of Tob1 sensitizes breast cancer cells to ionizing radiation.
OBJECTIVE
To investigate the effect of the Tob1 gene, a member of the Transducing Molecule of ErbB2/B-cell Translocation Ggene (TOB/BTG) family, by using the adenovirus-mediated expression of Tob1 on radiosensitivity in a human breast cancer cell line MDA-MB-231.


METHODS
Cell survival was determined by clonogenic assay. Apoptosis was evaluated by DNA fragmentation gel electrophoresis and terminal deoxynucleotidyl transferase-mediated nick end labeling assay. Protein expression was analyzed by Western blot assay and DNA repair was measured by a host cell reactivation assay.


RESULTS
We demonstrated that pre-irradiation treatment with Ad5-Tob1 significantly increased radiosensitivity, accompanying the increased induction of apoptosis and the repression of DNA damage repair. Furthermore, Ad5-Tob1-mediated radiosensitivity correlates with the upregulation of the pro-apoptotic protein Bax and the downregulation of several DNA double strand break repair proteins, including DNA-dependent protein kinases, Ku70 and Ku80, and X-ray-sensitive complementation group 4.


CONCLUSIONS
Tob1, as a new radiosensitizer, is a new target in the radiotherapy of breast cancer via increasing apoptosis and suppressing DNA repair.
Jiao
Yang
Y
School of Radiology and Public Health, Soochow University, Suzhou 215123, China.
Ge
Chun-Min
CM
Meng
Qing-Hui
QH
Cao
Jian-Ping
JP
Tong
Jian
J
Fan
Sai-Jun
SJ
D000256:Adenoviridae / Q000235:genetics*; D034961:Antigens, Nuclear / Q000378:metabolism; D017209:Apoptosis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002588:Cesium Radioisotopes; D004260:DNA Repair / Q000528:radiation effects; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000378:metabolism; D011839:Radiation, Ionizing; D011838:Radiation-Sensitizing Agents / Q000378:metabolism; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D034961:Antigens, Nuclear; D002588:Cesium Radioisotopes; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D011838:Radiation-Sensitizing Agents; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins; C101467:XRCC4 protein, human; D051028:bcl-2-Associated X Protein; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen