Early growth responsive gene 3 (EGR3) is a zinc-finger
transcription factor and plays important roles in cellular growth and differentiation. We recently demonstrated
estrogen-mediated induction of EGR3 in
breast carcinoma cells. However, EGR3 has not yet been examined in
breast carcinoma tissues and its significance remains unknown. Therefore, in this study, we examined
biological functions of EGR3 in the
breast carcinoma by immunohistochemistry, in vitro study, and nude mouse xenograft model. EGR3 immunoreactivity was detected in
carcinoma cells in 99 (52%) out of 190
breast carcinoma tissues and was associated with the
mRNA level. EGR3 immunoreactivity was positively associated with lymph node status, distant
metastasis into other organs,
estrogen receptor alpha, or EGR3 immunoreactivity in asynchronous recurrent lesions in the same patients, and was negatively correlated with tubule formation. EGR3 immunoreactivity was significantly associated with an increased risk of recurrence and adverse clinical outcome by both uni- and multivariate analyses. Egr3-expressing transformant cell lines derived from MCF-7 Tet-Off cells (Eg-10 and Eg-11) significantly enhanced the migration and invasion properties according to the treatment of doxycyclin, but did not significantly change the cell proliferation. Moreover, Eg-11 cells injected into athymic mice irregularly invaded into the adjacent peritumoral tissues, although Clt-7, which was stably transfected with empty vector as a control, demonstrated a well-circumscribed
tumor. Eg-11 cells were significantly associated with invasive components and less tubule formation in the xenograft model. These results suggest that EGR3 plays an important role in
estrogen-meditated invasion and is an independent prognostic factor in
breast carcinoma.