Differential effect of phosphorylation-defective survivin on radiation response in estrogen receptor-positive and -negative breast cancer.
Differential effect of phosphorylation-defective survivin on radiation response in estrogen receptor-positive and -negative breast cancer.
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DOI：
10.1371/journal.pone.0120719
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Woodward WA
中科院分区：
文献类型：
--
作者：
Debeb BG;Smith DL;Li L;Larson R;Xu W;Woodward WA
Survivin是凋亡抑制蛋白家族的重要成员之一，由于其在肿瘤中的普遍过表达，被认为是一个有前途的治疗靶点。存活素通过其在细胞凋亡、细胞分裂和DNA损伤反应中的作用参与细胞辐射反应。在本研究中，对临床可用数据集的分析显示，生存素基因表达随乳腺癌分期而增加（p < 0.00001），并且与雌激素受体阳性癌症相比，雌激素受体阴性癌症中生存素基因表达显著更高（p = 9 e-46）。然而，生存素在雌激素受体阳性肿瘤中具有预后意义（p = 0.03），而在雌激素受体阴性肿瘤中则无预后意义（p = 0.28）。我们评估了生存素显性阴性突变体对雌激素受体阳性MCF 7和雌激素受体阴性SUM 149乳腺癌细胞系的集落形成（2D）和乳腺球形成（3D）效率以及辐射反应的影响。与对照MCF 7细胞相比，显性阴性存活素转导的细胞中的集落形成效率显著较低（0.42对0.58，p < 0.01），但与对照转导的SUM 149细胞相比，显性阴性群体中的集落形成效率显著较高（0.29对0.20，p < 0.01）。观察到乳房球形成效率的相似、非显著趋势。我们比较了在2D和3D培养条件下暴露于增加剂量的辐射后，稳定表达显性阴性生存素的细胞与其对照细胞系的辐射敏感性。我们发现，显性阴性群体在MCF 7细胞中具有辐射保护性，但与对照转导群体相比，在SUM 149细胞中具有辐射敏感性;此外，泰素与SUM 149中的生存素突变体具有协同作用，但与MCF 7无关。我们的数据表明，生存素调节影响雌激素受体阳性和雌激素受体阴性乳腺癌亚型的辐射反应不同，有待进一步研究。
Survivin is a key member of the inhibitor of apoptosis protein family, and is considered a promising therapeutic target due to its universal overexpression in cancers. Survivin is implicated in cellular radiation response through its role in apoptosis, cell division, and DNA damage response. In the present study, analysis of publically available data sets showed that survivin gene expression increased with breast cancer stage (p < 0.00001) and was significantly higher in estrogen receptor-negative cancers as compared to estrogen receptor-positive cancers (p = 9e-46). However, survivin was prognostic in estrogen receptor-positive tumors (p = 0.03) but not in estrogen receptor-negative tumors (p = 0.28). We assessed the effect of a survivin dominant-negative mutant on colony-formation (2D) and mammosphere-formation (3D) efficiency, and radiation response in the estrogen receptor-positive MCF7 and estrogen receptor-negative SUM149 breast cancer cell lines. The colony-formation efficiency was significantly lower in the dominant-negative survivin-transduced cells versus control MCF7 cells (0.42 vs. 0.58, p < 0.01), but it was significantly higher in dominant-negative population versus control-transduced SUM149 cells (0.29 vs. 0.20, p < 0.01). A similar, non-significant, trend in mammosphere-formation efficiency was observed. We compared the radiosensitivity of cells stably expressing dominant-negative survivin with their controls in both cell lines under 2D and 3D culture conditions following exposure to increasing doses of radiation. We found that the dominant-negative populations were radioprotective in MCF7 cells but radiosensitive in SUM149 cells compared to the control-transduced population; further, Taxol was synergistic with the survivin mutant in SUM149 but not MCF7. Our data suggests that survivin modulation influences radiation response differently in estrogen receptor-positive and estrogen receptor-negative breast cancer subtypes, warranting further investigation.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
DOI：
10.1186/1756-9966-27-46
发表时间：
2008-09-25
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Peng XC;Yang L;Yang LP;Mao YQ;Yang HS;Liu JY;Zhang DM;Chen LJ;Wei YQ
通讯作者：
Wei YQ
DOI：
10.1002/stem.1219
发表时间：
2012-11
期刊：
Stem cells (Dayton, Ohio)
影响因子：
--
作者：
Debeb BG;Lacerda L;Xu W;Larson R;Solley T;Atkinson R;Sulman EP;Ueno NT;Krishnamurthy S;Reuben JM;Buchholz TA;Woodward WA
通讯作者：
Woodward WA
子宫内膜增生中生存素的异常表达：孕激素抵抗的另一种机制
影响因子：
7.5
作者：
Chen, Xiaojun;Zhang, Zhenbo;Zheng, Wenxin
通讯作者：
Zheng, Wenxin
DOI：
10.1016/j.ijrobp.2009.09.052
发表时间：
2010-03-01
影响因子：
7
作者：
Debeb, Bisrat G.;Xu, Wei;Mok, Henry;Li, Li;Robertson, Fredika;Ueno, Naoto T.;Reuben, Jim;Lucci, Anthony;Cristofanilli, Massimo;Woodward, Wendy A.
通讯作者：
Woodward, Wendy A.