Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation.
OBJECTIVE
To investigate the expression of TGF-beta3 in leiomyoma and myometrium as well as the effect of TGF-beta3 on the expression of fibronectin and on the proliferation of leiomyoma and myometrial cells.


METHODS
Observational and in vitro experimental study.


METHODS
University medical center.


METHODS
Women with (n = 18) leiomyoma.


METHODS
First TGF-beta3 mRNA and protein levels in myometrium and leiomyoma were measured, and then myometrial and leiomyoma cells in culture were treated with TGF-beta3.


METHODS
TGF-beta3 and fibronectin mRNA were evaluated by Northern analysis. Myometrial and leiomyoma cell proliferation was assessed with use of [(3)H]thymidine incorporation.


RESULTS
The TGF-beta3 mRNA level in the leiomyoma samples was 3.5-fold higher than in the myometrial samples. The highest TGF-beta3 mRNA level was observed in leiomyoma samples from midsecretory phase and was 5-fold higher than in proliferative phase samples. Fibronectin mRNA expression also was higher in the leiomyoma than in the myometrium. TGF-beta3 induced fibronectin expression in leiomyoma cells and directly stimulated myometrial and leiomyoma cell proliferation in cultures.


CONCLUSIONS
These findings suggest that TGF-beta3 may be mediating the growth-promoting effects of sex steroids on leiomyomas by playing a role in the fibrogenic process and cell proliferation that characterize these tumors.
Arici
A
A
Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA. aydin.arici@yale.edu
Sozen
I
I
D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D005353:Fibronectins / Q000096:biosynthesis*; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism*; D009215:Myometrium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism*
D005353:Fibronectins; D012739:Gonadal Steroid Hormones; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta