Concurrent down-regulation of Egr-1 and gelsolin in the majority of human breast cancer cells.
A growing body of evidence suggests that early growth response-1 (Egr-1), a transcription factor, may function as a tumor suppressor. The aim of this study was to gain more evidence to support the role of Egr-1 in the suppression of cancer cell growth and to examine the potential correlation between Egr-1 and gelsolin.


METHODS
Histochemical staining coupled with breast cancer tissue arrays were used to examine the expression levels of Egr-1 and gelsolin. Reporter assays and gel shift were used to study the transcriptional activity of Egr-1 on the regulation of gelsolin.


RESULTS
Our data showed that most normal mammary tissues expressed high levels of Egr-1, while the majority of breast cancer tissues expressed very small amounts of Egr-1. The expression pattern of Egr-1 in human breast cancer tissues was highly correlated with gelsolin expression. Induction of Egr-1 by serum stimulation accompanied the increase of gelsolin expression. In cells lacking the induction of Egr-1 in response to serum stimulation, gelsolin expression remained unchanged. Furthermore, gelsolin promoter activity was profoundly reduced in Egr-1 null mouse embryonic fibroblasts compared to Egr-1 wild-type mouse embryonic fibroblasts. Gel shift experiments indicated that Egr-1 can directly bind to the gelsolin promoter.


CONCLUSIONS
Our results suggest that Egr-1 may be an important breast cancer marker and that an as yet uncharacterized pathway involved in Egr-1 and gelsolin expression exists which leads to breast cancer cell development.
Liu
Jingbo
J
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Liu
Ya-Guang
YG
Huang
Ruochun
R
Yao
Chen
C
Li
Shiyong
S
Yang
Weimin
W
Yang
Dongzi
D
Huang
Ruo-Pan
RP
D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism*; D018260:Gelsolin / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D011401:Promoter Regions, Genetic / Q000235:genetics; D013997:Time Factors
C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D018260:Gelsolin