Hum. Reprod. Advance Access originally published online on April 13, 2006
Human Reproduction 2006 21(7):1869-1877; doi:10.1093/humrep/del035
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
A novel selective progesterone receptor modulator asoprisnil (J867) down-regulates the expression of EGF, IGF-I, TGF
3 and their receptors in cultured uterine leiomyoma cells
1 Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan and 2 TAP Pharmaceutical Products Inc., Lake Forest, IL, USA
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-Cho, Chuo-Ku, Kobe 650-0017, Japan. E-mail: maruo{at}kobe-u.ac.jp
BACKGROUND: This study was conducted to evaluate the effects of a novel selective progesterone receptor modulator (SPRM) asoprisnil on the expression of growth factors and their receptors and on growth factor-induced proliferation of cultured uterine leiomyoma and matching myometrial cells. METHODS: The expression of epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I) and transforming growth factor (TGF
3) was assessed by immunocytochemistry and semi-quantitative RT–PCR. The expression of phosphorylated EGF receptor (p-EGFR), IGF-I receptor 
subunit (IGF-IR) and phosphorylated TGF receptor type II (p-TGF RII) was assessed by Western blot analysis. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay. RESULTS: Treatment with 10–7 M asoprisnil decreased EGF, IGF-I and TGF3 mRNA and protein expression as well as p-EGFR, IGF-IR and p-TGF RII protein expression in leiomyoma cells cultured for 72 h. EGF (100 ng/ml), IGF-I (100 ng/ml) and TGF3 (10 ng/ml) increased the number of viable leiomyoma cells cultured for 72 h, whereas the concomitant treatment with 10–7 M asoprisnil antagonized the growth factor-induced increase in leiomyoma cell proliferation. In cultured myometrial cells, however, asoprisnil affected neither the growth factor and their receptor expression nor the cell proliferation. CONCLUSION: Asoprisnil inhibits the expression of EGF, IGF-I, TGF3 and their receptors in cultured leiomyoma cells without affecting their expressions in myometrial cells.
Key words:
asoprisnil/epidermal growth factor/insulin-like growth factor-I/leiomyoma/selective progesterone receptor modulator/transforming growth factor 3
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. Tropeano, S. Amoroso, and G. Scambia Non-surgical management of uterine fibroids Hum. Reprod. Update, May 1, 2008; 14(3): 259 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Morikawa, N. Ohara, Q. Xu, K. Nakabayashi, D. A. DeManno, K. Chwalisz, S. Yoshida, and T. Maruo Selective progesterone receptor modulator asoprisnil down-regulates collagen synthesis in cultured human uterine leiomyoma cells through up-regulating extracellular matrix metalloproteinase inducer Hum. Reprod., April 1, 2008; 23(4): 944 - 951. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ohara, A. Morikawa, Wei Chen, Jiayin Wang, D. A. DeManno, K. Chwalisz, and T. Maruo Comparative Effects of SPRM Asoprisnil (J867) on Proliferation, Apoptosis, and the Expression of Growth Factors in Cultured Uterine Leiomyoma Cells and Normal Myometrial Cells Reproductive Sciences, December 1, 2007; 14(8_suppl): 20 - 27. [Abstract] [PDF]
|
|
|
|
 |
|
 M. H. Hassan, S. A. Salama, H. M. M. Arafa, F. M. A. Hamada, and A. Al-Hendy Adenovirus-Mediated Delivery of a Dominant-Negative Estrogen Receptor Gene in Uterine Leiomyoma Cells Abrogates Estrogen- and Progesterone-Regulated Gene Expression J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3949 - 3957. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Xu, N. Ohara, J. Liu, K. Nakabayashi, D. DeManno, K. Chwalisz, S. Yoshida, and T. Maruo Selective progesterone receptor modulator asoprisnil induces endoplasmic reticulum stress in cultured human uterine leiomyoma cells Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1002 - E1011. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sasaki, N. Ohara, Q. Xu, J. Wang, D. A. DeManno, K. Chwalisz, S. Yoshida, and T. Maruo A Novel Selective Progesterone Receptor Modulator Asoprisnil Activates Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL)-Mediated Signaling Pathway in Cultured Human Uterine Leiomyoma Cells in the Absence of Comparable Effects on Myometrial Cells J. Clin. Endocrinol. Metab., February 1, 2007; 92(2): 616 - 623. [Abstract] [Full Text] [PDF]
|
|