Early growth response-2 expression in uterine leiomyoma cells: regulation and function

作者:Yin Ping; Navarro Antonia; Fang Feng; Xie Anna; Coon John S; Richardson Carrie; Bulun Serdar E*
来源:Fertility and Sterility, 2011, 96(2): 439-444.
DOI:10.1016/j.fertnstert.2011.05.062

摘要

Objective: To investigate the regulation of early growth response-2 (Egr-2) by transforming growth factor beta 3 (TGF-beta 3) and its functions in cultured human uterine leiomyoma smooth muscle cells. Design: Laboratory research. Setting: Academic medical center. Patient(s): Primary leiomyoma cells from patients with symptomatic leiomyomata. Intervention(s): Tissue culture followed by RNA and protein analysis. Main Outcome Measure(s): Cell proliferation, alteration in extracellular matrix component expression. Result(s): In vivo mRNA levels of Egr-2 were statistically significantly higher in leiomyoma tissues compared with matched myometrial tissues, and showed a statistically significant correlation with TGF-beta 3 messenger RNA (mRNA) levels in leiomyoma tissues. In primary leiomyoma smooth muscle cells, TGF-beta 3 statistically significantly induced Egr-2 gene expression in a dose-dependent and time-dependent manner. Small interfering RNA (siRNA) knockdown of Egr-2 markedly increased the level of the proliferation marker proliferating cell nuclear antigen and the expression of proto-oncogene c-myc. On the other hand, ablation of Egr-2 stimulated collagen-1A1 and collagen-3A1 transcription and inhibited dermatopontin gene expression. However, the mRNA levels of alpha-smooth muscle actin and fibronectin were not affected by Egr-2 knockdown. Conclusion(s): We demonstrated that TGF-beta 3 regulated Egr-2 gene expression and presented evidence that Egr-2 decreases collagen production and stimulates dermatopontin gene expression. (Fertil Steril (R) 2011;96:439-44.