Inhibition of RelB by 1,25-dihydroxyvitamin D3 promotes sensitivity of breast cancer cells to radiation.
Inhibition of RelB by 1,25-dihydroxyvitamin D3 promotes sensitivity of breast cancer cells to radiation.
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DOI：
10.1002/jcp.21765
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发表时间：
2009-09
影响因子：
5.6
通讯作者：
Sonenshein, Gail E.
中科院分区：
文献类型：
--
作者：
Mineva, Nora D.;Wang, Xiaobo;Yang, Sanghwa;Ying, Haoqiang;Xiao, Zhi-Xiong J.;Holick, Michael F.;Sonenshein, Gail E.
研究表明，乳腺癌细胞中NF-κB、c-Rel和RelA亚基的异常组成表达可促进其存活。最近，我们证明了侵袭性乳腺癌组成性地表达高水平的RelB亚基，它通过诱导BCL2基因促进其更具侵袭性的表型。由于这些癌症经常对治疗产生抗药性，我们在这里测试了RelB促进其生存的假设。高RelB表达的Hs578T和MDA-MB-231乳腺癌细胞比低RelB表达的MCF7和ZR-75细胞对γ辐射的抵抗更强。在Hs578T中敲低RelB导致对γ辐照的存活率降低，而相反，在MCF7细胞中异位表达RelB可保护这些细胞免受辐射。用化疗药物阿霉素治疗Hs578T或MCF7细胞也获得了类似的数据。高水平的血清25-羟基维生素D与降低乳腺癌风险和死亡率有关，尽管其保护作用的机制尚未阐明。1,25-二羟基维生素D3治疗Hs578T和Her-2/新驱动的NF639细胞，降低RelB/ RelB基因表达和促生存靶点Survivin、MnSOD和Bcl-2水平，同时增加它们对γ辐照的敏感性。因此，促进乳腺癌细胞存活和更高侵袭性表型的RelB是1,25-二羟维生素D3的靶标，为25-羟维生素D在乳腺癌患者中观察到的保护作用提供了一种机制。
Aberrant constitutive expression of the NF-κB c-Rel and RelA subunits in breast cancer cells was shown to promote their survival. Recently, we demonstrated that aggressive breast cancers constitutively express high levels of the RelB subunit, which promotes their more invasive phenotype via induction of the BCL2 gene. As these cancers are frequently resistant to therapy, here we tested the hypothesis that RelB promotes their survival. High RelB expressing Hs578T and MDA-MB-231 breast cancer cells were more resistant to γ-radiation than MCF7 and ZR-75 cells, which express lower RelB levels. Knockdown of RelB in Hs578T led to decreased survival in response to γ-irradiation, while conversely ectopic expression of RelB in MCF7 cells protected these cells from radiation. Similar data were obtained upon treatment of Hs578T or MCF7 cells with the chemotherapeutic agent doxorubicin. High serum levels of 25-hydroxyvitamin D are associated with decreased breast cancer risk and mortality, although, the mechanism of its protective action has not been elucidated. Treatment of Hs578T and Her-2/neu-driven NF639 cells with 1,25-dihydroxyvitamin D3 decreased RelB/RELB gene expression and levels of pro-survival targets Survivin, MnSOD and Bcl-2, while increasing their sensitivity to γ-irradiation. Thus, RelB, which promotes survival and a more highly invasive phenotype of breast cancer cells, is a target of 1,25-dihydroxyvitamin D3, providing one mechanism for the observed protective role of 25-hydroxyvitamin D in patients with breast cancer.
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影响因子：
5.3
作者：
Demicco, EG;Kavanagh, KT;Sonenshein, GE
通讯作者：
Sonenshein, GE
影响因子：
3.8
作者：
Bertone-Johnson, ER;Chen, WY;Hankinson, SE
通讯作者：
Hankinson, SE
影响因子：
4.8
作者：
Narvaez, CJ;Welsh, J
通讯作者：
Welsh, J
影响因子：
8.8
作者：
通讯作者：
--
影响因子：
8
作者：
Bren, GD;Solan, NJ;Paya, CV
通讯作者：
Paya, CV