New potential regulators of uterine leiomyomata from DNA arrays: The ionotropic glutamate receptor GluR2

Abstract In the post-Genome era, new concepts emerge about the growth regulation of uterine leiomyomata. Screening of leiomyoma and myometrial tissues with DNA arrays revealed numerous genes up-regulated in leiomyomata that were not known to be expressed in the human uterus. GluR2, a subunit of a ligand-gated cation channel, is up-regulated in leiomyomata relative to myometrium by 15- to 30-fold at the protein and mRNA level and is localized in endothelial cells. GluR2 pre-mRNA in leiomyoma and myometrial tissues is nearly 100% edited at the Q/R site, indicative of low Ca 2+ permeability of the ion channels. In spontaneous leiomyomata in women or leiomyomata induced in the guinea pig model, there is a likely synergism linking increased production of estradiol and all- trans retinoic acid with up-regulation of nuclear receptor PPARγ and RXRα proteins to support tumor growth. GluR2 might be coupled to this synergism directly or via interleukin-17B, kinesin KIF5 or related genes also up-regulated in leiomyomata. GluR antagonists should be tested as inhibitors of leiomyoma growth.