Médale-Giamarchi Claire, Lajoie-Mazenc Isabelle, Malissein Emilie, Meunier Elise, Couderc Bettina, Bergé Yann, Filleron Thomas, Keller Laura, Marty Claudine, Lacroix-Triki Magali, Dalenc Florence, Doisneau-Sixou Sophie F, Favre Gilles
Breast Cancer Res. 2013 Jan 22;15(1):R6. doi: 10.1186/bcr3377.
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.
据报道，RhoB对癌症病理生理学具有正负两方面的影响，但对其在乳腺癌中的作用的理解仍不完整。对Oncomine数据库数据的分析显示，RhoB表达与雌激素受体α（ERα）和孕激素受体（PR）的阳性表达之间呈正相关。
我们对由113名患者组成的队列构建的组织芯片进行分析，验证了这一发现，然后在人类细胞模型中进行研究。
我们发现组织中RhoB表达与ERα和PR表达密切相关，与肿瘤分级、肿瘤大小和有丝分裂计数呈负相关。在人乳腺癌细胞系中，RhoB衰减与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表达，控制其蛋白质和mRNA水平，并且RhoB通过增强ERα和其他主要共调节因子向PR基因启动子的募集来调节PR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与ERα之间的相互作用，雌激素处理导致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发挥促进ERα和PR表达的正向功能。
