Concurrent down-regulation of Egr-1 and gelsolin in the majority of human breast cancer cells.

Abstract

UNLABELLED:

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.

MATERIALS AND 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.

CONCLUSION:

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.

• Authors: Jingbo Liu, Ya-Guang Liu, Ruochun Huang, Chen Yao, Shiyong Li, Weimin Yang, Dongzi Yang, Ruo-Pan Huang
• Journal: Cancer genomics & proteomics (Cancer Genomics Proteomics) 2007 Nov-Dec Vol. 4 Issue 6 Pg. 377-85 ISSN: 1109-6535 [Print] Greece
• PMID: 18204200 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• EGR1 protein, human
• Early Growth Response Protein 1
• Gelsolin

Topics

• Animals
• Binding Sites
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Down-Regulation
• Early Growth Response Protein 1 (genetics, metabolism)
• Gelsolin (genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Mice
• Promoter Regions, Genetic (genetics)
• Time Factors