The expression of Abl interactor 2 in leiomyoma and myometrium and regulation by GnRH analogue and transforming growth factor-beta.
The expression of Abl interactor 2 in leiomyoma and myometrium and regulation by GnRH analogue and transforming growth factor-beta.
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Abl 相互作用蛋白 2 在平滑肌瘤和子宫肌层中的表达以及 GnRH 类似物和转化生长因子-β 的调节。
DOI：
10.1093/humrep/del011
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Chegini,Nasser
中科院分区：
文献类型：
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作者：
Luo,Xiaoping;Levens,Eric;Williams,RStan;Chegini,Nasser
背景技术背景：Abelson（Abl）interactor 2（Abi-2）被认为是细胞/组织结构组织的关键调节因子，并且在平滑肌瘤中差异表达。本研究的目的是评估月经周期和GnRH类似物（GnRHa）治疗后子宫肌瘤/肌层中Abi-2的表达，以及转化生长因子（TGF）-β1对子宫肌瘤和肌层平滑肌细胞（LSMC和MSMC）的调节。方法：我们使用实时PCR、蛋白质印迹和免疫组织化学方法来确定Abi-2在配对的子宫肌瘤和肌层（n= 27）中的表达，这些子宫肌瘤和肌层来自月经周期的增殖期（n= 8）和分泌期（n= 12）以及来自接受GnRHa治疗的患者（n= 7）。在LSMC和MSMC中测定TGF-β1（2.5 ng/ml）和GnRHa（0.1 µM）对Abi-2表达的时间依赖性作用。研究结果：与子宫肌层相比，子宫肌瘤在月经周期的增殖期表达更高水平的Abi-2，而在分泌期则无，GnRHa治疗后表达显著降低（P< 0.05）。Western blotting显示，在平滑肌瘤/子宫肌层组织提取物中，Abi-2蛋白表达的趋势相似，其免疫定位于LSMC和MSMC、结缔组织成纤维细胞和动脉壁。TGF-β1（2.5 ng/ml）可增加LSMC和MSMC中Abi-2的表达，GnRHa（0.1 µM）可抑制LSMC和MSMC中Abi-2的表达，且呈时间和细胞依赖性，分别用Smad 3 SiRNA和MEK-1/2抑制剂U 0126预处理可逆转其作用。结论：基于月经周期依赖性表达、GnRHa治疗的影响以及TGF-β在LSMC/MSMC中的调节，我们得出结论，Abi-2可能在平滑肌瘤生长和消退过程中的细胞/组织结构组织中具有关键调节功能。
BACKGROUND: Abelson (Abl) interactor 2 (Abi-2) has been considered as a key regulator of cell/tissue structural organization and is differentially expressed in leiomyomas. The objective of this study was to evaluate the expression of Abi-2 in leiomyoma/myometrium during the menstrual cycle and following GnRH analogue (GnRHa) therapy, as well as regulation by transforming growth factor (TGF)-β1 in leiomyoma and myometrial smooth muscle cells (LSMC and MSMC). METHODS: We used real-time PCR, Western blotting and immunohistochemistry to determine the expression of Abi-2 in paired leiomyoma and myometrium (n= 27) from proliferative (n= 8) and secretory (n= 12) phases of the menstrual cycle and from patients who received GnRHa therapy (n= 7). Time-dependent action of TGF-β1 (2.5 ng/ml) and GnRHa (0.1 µM) on Abi-2 expression was determined in LSMC and MSMC. RESULTS: Leiomyomas express elevated levels of Abi-2 as compared with myometrium from the proliferative but not the secretory phase of the menstrual cycle, with a significant reduction following GnRHa therapy (P< 0.05). Western blotting showed a similar trend in Abi-2 protein expression in leiomyoma/myometrial tissue extracts, which was immunolocalized in LSMC and MSMC, connective tissue fibroblasts and arterial walls. The expression of Abi-2 in LSMC and MSMC was increased by TGF-β1 (2.5 ng/ml) and was inhibited by GnRHa (0.1 µM) in a time- and cell-dependent manner, and pretreatment with Smad3 SiRNA and U0126, an MEK-1/2 inhibitor, respectively, reversed their actions. CONCLUSION: Based on the menstrual cycle-dependent expression, the influence of GnRHa therapy, and regulation by TGF-β in LSMC/MSMC, we conclude that Abi-2 may have a key regulatory function in leiomyomas cellular/tissue structural organization during growth and regression.