The expression of Abl interactor 2 in leiomyoma and myometrium and regulation by GnRH analogue and transforming growth factor-β

• Published in: Human reproduction (Oxford) 2006-06, Vol.21 (6), p.1380-1386
• Main Authors: Luo, Xiaoping, Levens, Eric, Williams, R. Stan, Chegini, Nasser
• Format: Article
• Language: English
• Subjects: Abi-2; Adaptor Proteins, Signal Transducing - biosynthesis; Adult; Biological and medical sciences; Cell Proliferation; Female; gene expression; Gene Expression Regulation, Neoplastic; GnRH analogue; Gonadotropin-Releasing Hormone - analogs & derivatives; Gynecology. Andrology. Obstetrics; Humans; leiomyoma; Leiomyoma - metabolism; MAP Kinase Signaling System; Medical sciences; Menstrual Cycle; Myocytes, Smooth Muscle - metabolism; Myometrium - metabolism; Myometrium - pathology; TGF-β; Transforming Growth Factor beta - metabolism; Uterine Neoplasms - metabolism
• ISSN: 0268-1161; 1460-2350
• DOI: 10.1093/humrep/del011

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.