A novel selective progesterone receptor modulator asoprisnil (J867) down-regulates the expression of EGF, IGF-I, TGFbeta3 and their receptors in cultured uterine leiomyoma cells.

Abstract

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 (TGFbeta3) was assessed by immunocytochemistry and semi-quantitative RT-PCR. The expression of phosphorylated EGF receptor (p-EGFR), IGF-I receptor alpha subunit (IGF-IRalpha) and phosphorylated TGFbeta receptor type II (p-TGFbeta 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 TGFbeta3 mRNA and protein expression as well as p-EGFR, IGF-IRalpha and p-TGFbeta RII protein expression in leiomyoma cells cultured for 72 h. EGF (100 ng/ml), IGF-I (100 ng/ml) and TGFbeta3 (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, TGFbeta3 and their receptors in cultured leiomyoma cells without affecting their expressions in myometrial cells.

• Authors: Jiayin Wang, Noriyuki Ohara, Zhuo Wang, Wei Chen, Akira Morikawa, Hiroko Sasaki, Deborah A DeManno, Kristof Chwalisz, Takeshi Maruo
• Journal: Human reproduction (Oxford, England) (Hum Reprod) Vol. 21 Issue 7 Pg. 1869-77 (Jul 2006) ISSN: 0268-1161 [Print] England
• PMID: 16613890 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Estrenes
• Oximes
• Proteoglycans
• Receptors, Growth Factor
• Receptors, Progesterone
• Receptors, Transforming Growth Factor beta
• Transforming Growth Factor beta
• betaglycan
• Epidermal Growth Factor
• Insulin-Like Growth Factor I
• asoprisnil
• ErbB Receptors
• Receptor, IGF Type 1

Topics

• Adult
• Blotting, Western
• Cell Proliferation (drug effects)
• Cells, Cultured
• Down-Regulation
• Epidermal Growth Factor (biosynthesis)
• ErbB Receptors (biosynthesis)
• Estrenes (pharmacology)
• Female
• Gene Expression (drug effects)
• Humans
• Insulin-Like Growth Factor I (biosynthesis)
• Leiomyoma (metabolism)
• Middle Aged
• Myometrium (cytology)
• Oximes (pharmacology)
• Proteoglycans (biosynthesis)
• Receptor, IGF Type 1 (biosynthesis)
• Receptors, Growth Factor (biosynthesis)
• Receptors, Progesterone (drug effects)
• Receptors, Transforming Growth Factor beta (biosynthesis)
• Reverse Transcriptase Polymerase Chain Reaction
• Transforming Growth Factor beta (biosynthesis)
• Tumor Cells, Cultured
• Uterine Neoplasms (metabolism)