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 (E
2), 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 [
6‐
8]. As a Rho protein, RhoB cycles between GTP and GDP bound states, forming interactions with a variety of effectors that modulate activity and influence important processes in cancer [
9]. RhoB, in contrast to its relatives RhoA and RhoC, has been shown to function as a tumor suppressor gene on the basis of investigations of genetically RhoB-deficient strains [
10] and in human cancer cells [
11‐
13]. RhoB is an immediate early response gene that is induced by a variety of stimuli, including growth factors [
6,
14‐
21]. Although no mutation of Rho GTPases have been detected in human tumors, a correlation has been demonstrated between Rho protein overexpression and poor clinical outcome in breast cancers [
22]. RhoB overexpression has been correlated to disease progression [
23], although this is a controversial issue [
24], and overexpression of guanine exchange factors (GEF) for Rho GTPases have been correlated to prognosis in breast cancers [
25]. Indeed, breast tumor progression is accompanied by a decrease in expression of the pro-oncogenic RhoGEF Tiam1 [
26]. Moreover, expression of Rho-GDI α, a negative regulator of Rho proteins, is reported to correlate with the outcome of patients with breast cancer treated by adjuvant chemotherapy [
27]. From a molecular point of view, scaffold proteins involved in Rho functions, such as Rho-GDI or Dblx, have been observed as part of ERα-containing complexes [
28,
29] with direct interaction between ERα and Rho-GDI [
30].
Besides the suggested specific involvement of RhoB in ER signaling, there have been no detailed investigations in breast cancer cells, including the assessment of any correlation with the expression of hormone receptors in tumors. A major goal of the present study was therefore to determine the involvement of RhoB in hormone-dependent breast cancers and to investigate hypothesized crosstalks between RhoB and ERα signaling.