title: Tamoxifen downregulates TGF-beta production in keloid fibroblasts.
abstract: Keloids occur only in humans and are characterized by fibroblast overproduction of collagen types I and III. Keloid fibroblasts have been shown to make elevated levels of transforming growth factor beta (TGF-beta), a growth factor known to promote extracellular matrix production and fibrosis. Thus, the pathophysiology underlying keloid formation may be driven by the biological activity of TGF-beta. Tamoxifen, a synthetic, nonsteroidal antiestrogen has been shown to inhibit keloid fibroblast proliferation and decrease collagen production. The purpose of this study was to determine if a mechanism by which tamoxifen decreases keloid collagen production is through a downregulation of TGF-beta. Through a luciferase TGF-beta bioassay we found that 4 microM of tamoxifen generated a 49% reduction in total TGF-beta activity and 8 microM generated an 85% reduction compared with controls. Thus we propose that one of the mechanisms by which tamoxifen decreases keloid fibroblast collagen synthesis is by decreasing TGF-beta production.
authors.affiliation: Department of Surgery, New York University Medical Center, NY 10016, USA.
authors.forename: D
authors.initials: D
authors.lastname: Chau
authors.forename: J S
authors.initials: JS
authors.lastname: Mancoll
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: L G
authors.initials: LG
authors.lastname: Phillips
authors.forename: G K
authors.initials: GK
authors.lastname: Gittes
authors.forename: M T
authors.initials: MT
authors.lastname: Longaker
mesh_terms: D018929:Cell Culture Techniques; D015536:Down-Regulation; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007627:Keloid; D008156:Luciferases; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D004965:Estrogen Antagonists; D016212:Transforming Growth Factor beta; D013629:Tamoxifen; D008156:Luciferases