Rad51 supports triple negative breast cancer metastasis.
Rad51 supports triple negative breast cancer metastasis.
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DOI：
10.18632/oncotarget.1923
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发表时间：
2014-05-30
期刊：
影响因子：
--
通讯作者：
Khanna KK
中科院分区：
文献类型：
--
作者：
Wiegmans AP;Al-Ejeh F;Chee N;Yap PY;Gorski JJ;Da Silva L;Bolderson E;Chenevix-Trench G;Anderson R;Simpson PT;Lakhani SR;Khanna KK
与对家族性乳腺癌的广泛研究相比，目前尚不清楚DNA双链断裂(DSB)修复基因缺陷是否在散发性乳腺癌的发生和发展中发挥作用。我们对235例散发性乳腺肿瘤进行了免疫组织化学分析。这一分析表明，在乳腺癌进展和转移过程中，RAD51的表达增加，当RAD51被解除调控时，RAD51具有致癌作用。随后RAD51基因的敲除抑制了癌细胞在体外的迁移，并减少了体内同基因小鼠模型中的原发肿瘤生长。RAD51的缺失不仅抑制了同基因小鼠的相关转移，也抑制了人类移植瘤的转移，并改变了癌细胞的转移基因表达谱，这与抑制远处转移是一致的。这首次证明了RAD51的一种新功能，该功能可能是RAD51过度表达患者发生远处转移的基础。RAD51是治疗转移性三阴性乳腺癌的潜在生物标志物和有吸引力的药物靶点，能够延长患者不到6个月的生存期。
In contrast to extensive studies on familial breast cancer, it is currently unclear whether defects in DNA double strand break (DSB) repair genes play a role in sporadic breast cancer development and progression. We performed analysis of immunohistochemistry in an independent cohort of 235 were sporadic breast tumours. This analysis suggested that RAD51 expression is increased during breast cancer progression and metastasis and an oncogenic role for RAD51 when deregulated. Subsequent knockdown of RAD51 repressed cancer cell migration in vitro and reduced primary tumor growth in a syngeneic mouse model in vivo. Loss of RAD51 also inhibited associated metastasis not only in syngeneic mice but human xenografts and changed the metastatic gene expression profile of cancer cells, consistent with inhibition of distant metastasis. This demonstrates for the first time a new function of RAD51 that may underlie the proclivity of patients with RAD51 overexpression to develop distant metastasis. RAD51 is a potential biomarker and attractive drug target for metastatic triple negative breast cancer, with the capability to extend the survival of patients, which is less than 6 months.
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RAD51的高级表达是非小细胞肺癌患者生存的独立预后标志。
影响因子：
8.8
作者：
Qiao, GB;Wu, YL;Yang, XN;Zhong, WZ;Xie, D;Guan, XY;Fischer, D;Kolberg, HC;Kruger, S;Stuerzbecher, HW
通讯作者：
Stuerzbecher, HW
影响因子：
5.6
作者：
Chipitsyna, G;Sawaya, BE;Amini, S
通讯作者：
Amini, S
影响因子：
64.8
作者：
Curtis, Christina;Shah, Sohrab P.;Chin, Suet-Feung;Turashvili, Gulisa;Rueda, Oscar M.;Dunning, Mark J.;Speed, Doug;Lynch, Andy G.;Samarajiwa, Shamith;Yuan, Yinyin;Graef, Stefan;Ha, Gavin;Haffari, Gholamreza;Bashashati, Ali;Russell, Roslin;McKinney, Steven;Langerod, Anita;Green, Andrew;Provenzano, Elena;Wishart, Gordon;Pinder, Sarah;Watson, Peter;Markowetz, Florian;Murphy, Leigh;Ellis, Ian;Purushotham, Arnie;Borresen-Dale, Anne-Lise;Brenton, James D.;Tavare, Simon;Caldas, Carlos;Aparicio, Samuel
通讯作者：
Aparicio, Samuel
影响因子：
8
作者：
Richardson, C;Stark, JM;Jasin, M
通讯作者：
Jasin, M
影响因子：
50.3
作者：
Gomis, Roger R.;Alarcon, Claudio;Massague, Joan
通讯作者：
Massague, Joan