Epidermal Growth Factor-containing Fibulin-like Extracellular Matrix Protein 1 Expression and Regulation in Uterine Leiomyoma

Objective: To determine the presence, differential expression, and regulation of epidermal growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1) in uterine leiomyomas.

Design: Laboratory in vivo and in vitro study with the use of human leiomyoma and myometrial tissue and primary cells.

Setting: Academic medical center.

Sample(s): Leiomyoma and myometrial tissue samples and cultured cells.

Intervention(s): 5-Aza-2'-deoxycytidine (5-aza-dC) treatment.

Main Outcome Measure(s): Fold-change difference between EFEMP1 and fibulin-3 expression in leiomyoma tissue and cells compared with matched myometrial samples, and fold-change difference in EFEMP1 expression with 5-Aza-dC treatment.

Result(s): In vivo, EFEMP1 expression was 3.19-fold higher in myometrial tissue than in leiomyoma tissue. EFEMP1 expression in vitro was 5.03-fold higher in myometrial cells than in leiomyoma cells. Western blot and immunohistochemistry staining of tissue and cells confirmed similar findings in protein expression. Treatment of leiomyoma cells with 5-Aza-dC resulted in increased expression of EFEMP1 in vitro.

Conclusion(s): The EFEMP1 gene and its protein product, fibulin-3, are both significantly down-regulated in leiomyoma compared with myometrium when studied both in vivo and in vitro. The increase in EFEMP1 expression in leiomyoma cells with 5-Aza-dC treatment suggest that differential methylation is responsible, in part, for the differences seen in gene expression.