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

Abstract

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)-beta1 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-beta1 (2.5 ng/ml) and GnRHa (0.1 microM) 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-beta1 (2.5 ng/ml) and was inhibited by GnRHa (0.1 microM) 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-beta in LSMC/MSMC, we conclude that Abi-2 may have a key regulatory function in leiomyomas cellular/tissue structural organization during growth and regression.

• Authors: Xiaoping Luo, Eric Levens, R Stan Williams, Nasser Chegini
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 21 Issue 6 Pg. 1380-6 (Jun 2006) ISSN: 0268-1161 [Print] England
• PMID: 16488906 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• ABI2 protein, human
• Adaptor Proteins, Signal Transducing
• Transforming Growth Factor beta
• Gonadotropin-Releasing Hormone

Topics

• Adaptor Proteins, Signal Transducing (biosynthesis)
• Adult
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic
• Gonadotropin-Releasing Hormone (analogs & derivatives)
• Humans
• Leiomyoma (metabolism)
• MAP Kinase Signaling System
• Menstrual Cycle
• Myocytes, Smooth Muscle (metabolism)
• Myometrium (metabolism, pathology)
• Transforming Growth Factor beta (metabolism)
• Uterine Neoplasms (metabolism)