New potential regulators of uterine leiomyomata from DNA arrays: the ionotropic glutamate receptor GluR2.
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 PPARgamma and RXRalpha 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.
Tsibris
John C M
JC
Department of Obstetrics and Gynecology, University of South Florida, 4 Columbia Drive, Room 524, Tampa, FL 33606, USA. jtsibris@hsc.usf.edu
Maas
Stefan
S
Segars
James H
JH
Nicosia
Santo V
SV
Enkemann
Steven A
SA
O'Brien
William F
WF
Spellacy
William N
WN
D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007889:Leiomyoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2