Rho GDP dissociation inhibitor beta (
Rho-GDI beta), an inhibitor of
Rho GTPases, is primarily expressed by hematopoietic cells but is also found in epithelial
cancer cells. Recently, we have identified
Rho-GDI beta as a target of the
transcription factor Ets1. Here, we show that, in
breast cancer cells, Ets1 regulates
Rho-GDI beta expression and binds to the upstream region of the
Rho-GDI beta gene. Furthermore, in primary
breast cancer,
Rho-GDI beta is coexpressed with Ets1. Studying the function of
Rho-GDI beta in
breast cancer, we found that a Rho-GD beta-specific
small interfering RNA increased cellular migration but also decreased the expression of
cyclooxygenase-2 (Cox-2) oncogene as shown by microarray, quantitative reverse transcription-PCR, and Western blot analyses. Further studies revealed that
Rho-GDI beta regulates Cox-2 gene at least partly on the transcriptional level, most likely by activating nuclear factor of activated T cells 1 (NFAT-1). Vav-1, an interaction partner of
Rho-GDI beta, was also found to interfere with Cox-2 expression and NFAT-1 cellular distribution, suggesting a cooperative action of
Rho-GDI beta and Vav-1 on Cox-2 expression. To explore the importance of
Rho-GDI beta for the survival of
breast cancer patients, two cohorts, including 263 and 117 patients, were analyzed for clinical outcome in relation to
Rho-GDI beta
RNA and
protein levels, respectively. Expression of
Rho-GDI beta was not associated with either disease-free or overall survival in the two patient population. Our data suggest that the expression of
Rho-GDI beta in
breast cancer is neither beneficial nor disadvantageous to the patient. This may be the net effect of two opposing activities of
Rho-GDI beta, one that suppresses
tumor progression by inhibiting migration and the other that stimulates it by enhancing Cox-2 expression.