Mol. Hum. Reprod. Advance Access published online on January 29, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah028
© 2004 by Oxford University Press
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1 Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA
* To whom correspondence should be addressed. E-mail: john.castellot{at}tufts.edu.
Uterine fibroids (leiomyomas) are a major women’s health problem. Currently, the standard for treatment remains hysterectomy, since no other treatment modalities can reduce both symptoms and recurrence. As leiomyomas are benign neoplasias of smooth muscle cells, we sought to understand the regulation of uterine smooth muscle cell mitogenesis by CCN5, a growth arrest-specific gene in vascular smooth muscle cells which is induced and maintained by heparin treatment. Using autologous human myometrial and leiomyoma smooth muscle cells, we demonstrate that the proliferation and motility of both cell types are inhibited by the overexpression of CCN5. Surprisingly, we show that even though CCN5 is induced by heparin in vascular smooth muscle cells, treatment with heparin does not induce CCN5 expression in human uterine smooth muscle cells. Furthermore, we examine CCN5 mRNA expression in 10 autologous pairs of human myometrial and leiomyoma tissues and determine that CCN5 is down-regulated in 100% of the leiomyoma tissues analysed when compared to their normal myometrial counterparts. Thus, our data strongly suggest that CCN5 may exert an important function in maintaining the normal uterine phenotype and that loss of the anti-proliferative protein CCN5 from normal myometrium may account, at least in part, for tumorigenesis.
Revised November 17, 2003
Accepted November 18, 2003
Article
The growth arrest-specific gene CCN5 is deficient in human leiomyomas and inhibits the proliferation and motility of cultured human uterine smooth muscle cells
2 Department of Animal Sciences, University of Illinois, 1207 West Gregory Drive, ASL 310, Urbana, IL 61801, USA
3 Program in Cell, Molecular, and Developmental Biology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA; Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, Massachusetts, USA; Department of Anatomy and Cellular Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
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