The expression of Smads and transforming growth factor beta receptors in leiomyoma and myometrium and the effect of gonadotropin releasing hormone analogue therapy

被引:64
作者
Chegini, N [1 ]
Luo, XP [1 ]
Ding, L [1 ]
Ripley, D [1 ]
机构
[1] Univ Florida, Dept OB GYN, Gainesville, FL 32610 USA
关键词
leiomyoma; myometrium; TGF-beta; TGF-beta receptor; Smads; GnRHa;
D O I
10.1016/j.mce.2003.08.007
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Gene microarray analysis indicated that several components of the transforming growth factor beta receptor (TGF-betaR) signaling pathway are differentially expressed in leiomyoma and myometrium. To validate the microarray results we evaluated the expression of Smads, intracellular proteins that transmit TGF-betaR signals, in leiomyoma and matched myometrium from untreated women, and women who received gonadotropin releasing hormone analogue (GnRHa) therapy. Semi-quantitative RT-PCR, Western blotting and immunohistochemistry indicate that leiomyoma and myometrium expresses receptor-activated Smad3, common Smad4 and inhibitory Smad7; with elevated expression of Smad3, Smad4 and phosphorylated Smad3 (pSmad3) as well as TGF-betaR type I and type II in leiomyoma compared to myometrium (P < 0.05). GnRHa therapy resulted in lowering of TGF-betaRs as well as Smad4 and pSmad3, with concurrent increased in Smad7 expression in both leiomyoma and myometrium compared to untreated group (P < 0.05). Immunohistochemically Smads and pSmad3 were localized in cytoplasmic/nuclear compartments of leiomyoma and myometrial smooth muscle cells and connective tissue fibroblasts, with alteration in their intensity (HScores) in GnRHa-treated group. In conclusion, the results indicates that leiomyoma and myometdum express all the components of TGF-betaR and Smads, and GnRHa therapy results in alteration of their expression further supporting the importance of TGF-beta system as key regulator of leiomyoma growth. (C) 2003 Elsevier Ireland Ltd. All rights reserved.
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页码:9 / 16
页数:8
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