Early growth responsive gene 3 in human breast carcinoma: a regulator of estrogen-meditated invasion and a potent prognostic factor

Early growth responsive gene3 (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 functionsofEGR3inthebreastcarcinomabyimmunohistochemistry,invitrostudy,andnudemouse 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 positivelyassociatedwithlymphnodestatus,distantmetastasisintootherorgans,estrogenreceptor a, or EGR3 immunoreactivity in asynchronous recurrent lesions in the same patients, and was negativelycorrelatedwithtubuleformation.EGR3immunoreactivitywassignificantlyassociatedwith 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) significantlyenhancedthemigrationandinvasionpropertiesaccordingtothetreatmentofdoxycyclin, butdidnotsignificantlychangethecellproliferation.Moreover,Eg-11cellsinjectedintoathymicmice irregularlyinvadedintotheadjacentperitumoraltissues,althoughClt-7,whichwasstablytransfected 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. Endocrine-Related Cancer (2007) 14 279‐292