The hormone-dependent nature of breast cancer and the important role of estrogen receptor alpha (ERα) in initiation and progression supported development of pharmacologic agents to either reduce circulating estrogen levels or modulate ERα functions [ 2, 3].
We hypothesized that the ability of RhoB to modulate ERα expression could control the major transcriptional functions of ERα.
Since estrogen activity can be modulated by agonists as well as by antagonists, compounds that interfere with ERα function have proved useful in the treatment and chemoprevention of ER-positive breast cancer [ 10].
Like Hakai, some ubiquitin ligases are reported to function as transcriptional regulators such as E2 ubiquitin ligase BRCA1 that modulate ERα transactivation [ 81], or RING finger LIM domain-interacting protein that enhanced the activation on targets genes mediated by ERα while it inhibits transcriptional activity of LIM-HD [ 82].
None of the tested FAs could modulate ERα recruitment to the pS2 promoter, whilst they increased ERβ recruitment to this promoter.
Additionally, ERβ is known to bind to ERα suppressing ERα function [ 19, 20].
Twelve of the MammaPrint™ genes are directly ERα responsive, indicating that MammaPrint™ assesses ERα function in breast cancer without considering ERα mRNA levels.
34 In summary, ERβ1 or ERβ2 appear to interfere with ERα function and downregulate ERα downstream genes.
Western blotting was also conducted to examine alterations in the expression of ERα and pathways that are associated with ERα function.
COUP-TFI and COUP-TFII are orphan nuclear receptors that can also act by modulating other nuclear receptors, including ERα, functioning selectively as a co-activator or a co-repressor [ 10] to control biological processes linked to cellular growth, migration, or angiogenesis and potentially contributing to cancer progression [ 10- 12].
