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The development of malignant tumors is the result of sequential genetic and epigenetic lesions that lead to alterations in a number of gene expressions, which are primarily controlled by transcription factors. A growing body of evidence suggests that early growth response-1 (Egr-1), a transcription factor, may function as a tumor suppressor. To gain more evidence to support the role of Egr-1 in the suppression of cancer cell growth, we examined the expression of Egr-1 in human breast cancer tissues. Our data showed that all normal mammary tissues expressed high levels of Egr-1, while most of the breast cancer tissues expressed very small amounts of Egr-1. The expression pattern of Egr-1 in human breast cancer tissues is highly correlated with gelsolin expression. Induction of Egr-1 by serum stimulation accompanies the increase of gelsolin expression. While 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 comparing with Egr-1 wild type mouse embryonic fibroblasts. Our results suggest that Egr-1 may be an important breast cancer marker and that there exists a potential new pathway involved in Egr-1 and gelsolin leading to breast cancer cell progression.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]