RhoB modifies estrogen responses in breast cancer cells by influencing expression of the estrogen receptor.
RhoB modifies estrogen responses in breast cancer cells by influencing expression of the estrogen receptor.
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DOI：
10.1186/bcr3377
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发表时间：
2013-01-22
期刊：
影响因子：
--
通讯作者：
Favre G
中科院分区：
文献类型：
--
作者：
Médale-Giamarchi C;Lajoie-Mazenc I;Malissein E;Meunier E;Couderc B;Bergé Y;Filleron T;Keller L;Marty C;Lacroix-Triki M;Dalenc F;Doisneau-Sixou SF;Favre G
据报道，RhoB对癌症病理生理产生积极和消极的影响，但对其在乳腺癌中的作用的理解仍然不完整。来自Oncomine数据库的数据分析显示，RhoB表达与雌激素受体α（ERα）和孕激素受体（PR）阳性之间呈正相关。这一发现通过我们对从113名患者的队列中构建的组织微阵列的分析得到了验证，然后在人类细胞模型中进行了研究。RhoB表达与ERα、PR表达密切相关，与肿瘤分级、肿瘤大小、核分裂数呈负相关。在人乳腺癌细胞系中，RhoB减弱与ERα和PR表达降低相关，而RhoB升高与ERα过表达相关。机制研究表明，RhoB调节ERα的表达，控制其蛋白和mRNA水平，RhoB通过加强ERα和其他主要辅助调节因子向PR基因启动子的募集来调节PR的表达。RhoB调节的一个主要结果是RhoB差异调节乳腺癌细胞系的增殖。有趣的是，我们记录了RhoB和ERα之间的串扰，雌激素治疗导致RhoB激活。综上所述，我们的研究结果提供了证据表明，在人类乳腺癌中，RhoB以与细胞增殖相关的方式促进ERα和PR的表达。
RhoB has been reported to exert positive and negative effects on cancer pathophysiology but an understanding of its role in breast cancer remains incomplete. Analysis of data from the Oncomine database showed a positive correlation between RhoB expression and positivity for both estrogen receptor alpha (ERα) and progesterone receptor (PR). This finding was validated by our analysis of a tissue microarray constructed from a cohort of 113 patients and then investigated in human cell models. We found that RhoB expression in tissue was strongly correlated with ERα and PR expression and inversely correlated with tumor grade, tumor size and count of mitosis. In human breast cancer cell lines, RhoB attenuation was associated with reduced expression of both ERα and PR, whereas elevation of RhoB was found to be associated with ERα overexpression. Mechanistic investigations suggested that RhoB modulates ERα expression, controlling both its protein and mRNA levels, and that RhoB modulates PR expression by accentuating the recruitment of ERα and other major co-regulators to the promoter of PR gene. A major consequence of RhoB modulation was that RhoB differentially regulated the proliferation of breast cancer cell lines. Interestingly, we documented crosstalk between RhoB and ERα, with estrogen treatment leading to RhoB activation. Taken together, our findings offer evidence that in human breast cancer RhoB acts as a positive function to promote expression of ERα and PR in a manner correlated with cell proliferation.
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影响因子：
4.1
作者：
Gampel, A;Mellor, H
通讯作者：
Mellor, H
影响因子：
4.8
作者：
Canguilhem, B;Pradines, A;Favre, G
通讯作者：
Favre, G
影响因子：
30.8
作者：
Carroll, Jason S.;Meyer, Clifford A.;Brown, Myles
通讯作者：
Brown, Myles
DOI：
10.1186/1477-7800-5-23
发表时间：
2008-10-16
期刊：
International seminars in surgical oncology : ISSO
影响因子：
--
作者：
Lane, Jane;Martin, Tracey A;Jiang, Wen G
通讯作者：
Jiang, Wen G
影响因子：
19
作者：
Guilluy C;Garcia-Mata R;Burridge K
通讯作者：
Burridge K