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Transforming growth factor-beta3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression
1Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut, USA. aydin.arici@yale.edu
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.
Design:
Observational and in vitro experimental study.
Setting:
University medical center.
Patient(S):
Women with (n = 18) leiomyoma.
Intervention(S):
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.
Main Outcome Measure(S):
TGF-beta3 and fibronectin mRNA were evaluated by Northern analysis. Myometrial and leiomyoma cell proliferation was assessed with use of [(3)H]thymidine incorporation.
Result(S):
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.
Conclusion(S):
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.