Adenovirus-mediated expression of Tob1 sensitizes breast cancer cells to ionizing radiation.

Abstract:

AIM: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. CONCLUSION:Tob1, as a new radiosensitizer, is a new target in the radiotherapy of breast cancer via increasing apoptosis and suppressing DNA repair.

journal_name

Acta Pharmacol Sin

authors

Jiao Y,Ge CM,Meng QH,Cao JP,Tong J,Fan SJ

doi

10.1111/j.1745-7254.2007.00647.x

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

1628-36

issue

10

eissn

1671-4083

issn

1745-7254

journal_volume

28

pub_type

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