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.

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.