Epidermal growth factor containing fibulin like extracellular matrix protein 1 EFEMP1 expression and regulation in uterine leiomyoma

Capsule:
Epidermal growth factor–containing fibulin-like extracellular matrix protein 1 gene expression and fibulin- 3 protein expression are significantly down-regulated in leiomyomas versus myometrium in vivo and in vitro. Differences in expression are partially due to differences in methylation status.

Authors:
Erica E. Marsh, M.D., M.S.C.I., Shani Chibber, M.S., Ju Wu, M.D., Kendra Siegersma, B.S., Julie Kim, Ph.D., Serdar Bulun, M.D.

Volume 105, Issue 4, Pages 1070-1075

Abstract:

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.

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