RhoB modifies estrogen responses in breast cancer cells by influencing expression of the estrogen receptor

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.Hormone therapy is recommended in breast cancers that express estrogen receptor alpha (ERα) and/or progesterone receptor (PR). This therapy is largely effective but there are nevertheless many cases of systemic resistance. A number of studies have addressed the question of the mechanisms of resistance to hormone therapy [1,2]. ERα transcriptional effects are not only determined by ligands as estradiol (E2), but also by crosstalk between ERα and growth factor signaling [3]. The hierarchy among these associations is not known and various growth factor receptors are likely to be required [3].Prenylated proteins such as Rho GTPases are key elements in growth factor signal transduction pathways [4]. A variety of growth factors present in the tumor microenvironment activate Rho proteins [5], especially RhoB [