Much of the work carried out by DTT is in support of the National Toxicology Program (NTP), an interagency partnership of the Food and Drug Administration, National Institute for Occupational Safety and Health, and NIEHS.
Molecular Pathogenesis Group
The role of growth factors in uterine leiomyoma development and growth has not been fully elucidated. It has been suggested that the ovarian steroid hormone-responsiveness of fibroids may be mediated, in part, by peptide growth factors that influence the proliferation of smooth muscle, fibroblasts and the vasculature. Genes of growth factors and growth factor receptors may be inducible by estrogen and/or progesterone, thus suggesting that growth factors may serve as paracrine, autocrine or intracrine mediators of estrogen stimulated growth.
Uterine leiomyomas may be the target of environmental chemicals whose biological effects are mediated through estrogen and/or progesterone receptors, and that too may be capable of induction of genes of growth factors and/or their receptors. Growth factors such as insulin-like growth factor (IGF)-I, IGF-II, epidermal growth factor (EGF), transforming growth factor-beta (TGF-β), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF; FGF-2), vascular endothelial growth factor (VEGF) and their respective receptors have been implicated or hypothesized to play a role in uterine leiomyoma growth.
Most studies, to date, have measured the increase or decrease of growth factor expression by mRNA or gene expression studies. Others have conducted receptor assays to assess receptor quantitation. There are few studies that evaluate and quantitate actual localization of growth factor peptides and receptors in uterine leiomyomas and matched myometrial samples using immunohistochemical techniques.
Our initial studies began by quantitation of differential immunoexpression of several growth factor peptides and their respective receptors in uterine leiomyomas and matched myometrial samples taken from women in the proliferative phase of the menstrual cycle.