B细胞易位基因2的表达水平对肿瘤细胞放射敏感性的影响  

Effect of B-cell translocation gene 2 alteration on radiosensitivity of cancer cells

作　　者：李敏[1] 孟庆慧[1] 胡旭东[1,2] 焦旸[1] 徐加英[1] 樊赛军[1,3] 

机构地区：[1]苏州大学医学部放射医学与公共卫生学院肿瘤放射生物学实验室,215123 [2]山东省肿瘤医院放疗科,济南250117 [3]中国医学科学院放射医学研究所,天津市分子核医学重点实验室,天津300192

出　　处：《国际放射医学核医学杂志》2013年第3期129-134,共6页International Journal of Radiation Medicine and Nuclear Medicine

基　　金：国家自然科学基金（81172127,81071906）

摘　　要：目的研究B细胞易位基因2（BTG2）表达水平的改变对肿瘤细胞放射敏感性的影响。方法通过pcDNA3．BTG2脂质体转染的方法提高细胞的BTG2的表达水平，利用噻唑蓝和细胞克隆形成实验研究细胞放射敏感性的改变，应用Westernblot方法研究蛋白表达水平的变化。结果噻唑蓝和细胞克隆形成实验结果显示，在不同剂量的1射线照射后，提高BTG2的表达水平可明显提高乳腺癌MCF．7和MDA．MB．231细胞的放射敏感性。免疫共沉淀．Westernblot实验结果显示BTG2蛋白与DNA损伤修复和抗氧化蛋白乳腺癌易感基因1（BRCA1）相互作用，形成复合物。高表达的BRCAl明显地抑制了BTG2高表达对乳腺癌细胞放射敏感性的调节作用，而降低BRCA1的表达水平则提高了BTG2对乳腺癌细胞放射敏感性的调节作用。另外，肺癌细胞放射敏感性与其所含的BRCAl的表达水平成反比，而与BTG2的表达水平成正比。结论BTG2的高表达明显提高了肿瘤细胞的放射敏感性，其机制可能与其同BRCAl形成复合物有关。Objective To investigate the effects of B-cell translocation gene 2 （BTG2） over- expression on the radiosensitivity of cancer cells. Methods Cancer cells with overexpression of BTG2 were established via stable transfection of full-length human BTG2 cDNA which was inserted into a mammalian expression plasmid pcDNA3 （pcDNA3-BTG2）. Cell survival was determined by thi- azolyl blue tetrazolium bromide （MTI＇） and clonogenic survival assays. Protein-protein interaction was performed by immune precipitation （IP）-Western blot assay. Protein expression was assayed by West- ern blot assay. Results As demonstrated in M33＂ assay and clonogenic survival assay, enforced expression of BTG2 significantly enhanced radiosenstivity of human breast cancer MCF-7 and MAD- MB-231 cells. The BTG2 protein was able to be determined in the breast cancer susceptibility genel （BRCA1） IP. Silence of BRCA1 enhanced the increased radiosensitivity by BTG2, however, co-over- expression of BRCA1 reduced the BTG2-mediated radiosenstivity. Finally, the radiosensitivity of lung cancer cell lines tested exhibited a positive relationship with the levels of BTG2 protein expression and a negative correlation with the levels of BRCA1 protein expression. Conclusion The present study further demonstrates that there is a significant relationship of radiosenstivity with BTG2 and BRCA1 expression, suggesting that BTG2 may be a new and important target in cancer radiotherapy via its binding to BRCA1.

关 键 词：肿瘤 辐射耐受性 B细胞易位基因2 基因 BRCA1 

分 类 号：R730[医药卫生—肿瘤]