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.
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.


CONCLUSIONS
Asoprisnil inhibits the expression of EGF, IGF-I, TGFbeta3 and their receptors in cultured leiomyoma cells without affecting their expressions in myometrial cells.
Wang
Jiayin
J
Department of Obstetrics and Gynecology, Kobe University Graduate School of Medicine, Kobe, Japan.
Ohara
Noriyuki
N
Wang
Zhuo
Z
Chen
Wei
W
Morikawa
Akira
A
Sasaki
Hiroko
H
DeManno
Deborah A
DA
Chwalisz
Kristof
K
Maruo
Takeshi
T
D000328:Adult; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000096:biosynthesis*; D066246:ErbB Receptors / Q000096:biosynthesis; D004963:Estrenes / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D007889:Leiomyoma / Q000378:metabolism*; D008875:Middle Aged; D009215:Myometrium / Q000166:cytology; D010091:Oximes / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D017978:Receptors, Growth Factor / Q000096:biosynthesis*; D011980:Receptors, Progesterone / Q000187:drug effects*; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000378:metabolism*
D004963:Estrenes; D010091:Oximes; D011509:Proteoglycans; D017978:Receptors, Growth Factor; D011980:Receptors, Progesterone; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; C488516:asoprisnil; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1