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

John C.M. Tsibris; Stefan Maas; James H. Segars; Santo V. Nicosia; Steven A. Enkemann; William F. O'Brien; William N. Spellacy

doi:10.1016/j.bbrc.2003.09.189

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

John C.M. Tsibris, Stefan Maas, James H. Segars, Santo V. Nicosia, Steven A. Enkemann, William F. O'Brien, William N. Spellacy

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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 Ca²⁺ 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.

Original language	English (US)
Pages (from-to)	249-254
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	312
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2003.09.189
State	Published - Dec 5 2003
Externally published	Yes

Keywords

AMPA receptors
Arrays
Glutamate receptors
Leiomyoma
Myometrium
Neovascularization
Uterine neoplasms

ASJC Scopus subject areas

Biophysics
Biochemistry
Molecular Biology
Cell Biology

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title = "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 Ca2+ 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.",

keywords = "AMPA receptors, Arrays, Glutamate receptors, Leiomyoma, Myometrium, Neovascularization, Uterine neoplasms",

author = "Tsibris, {John C.M.} and Stefan Maas and Segars, {James H.} and Nicosia, {Santo V.} and Enkemann, {Steven A.} and O'Brien, {William F.} and Spellacy, {William N.}",

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AU - Tsibris, John C.M.

AU - Maas, Stefan

AU - Segars, James H.

AU - Nicosia, Santo V.

AU - Enkemann, Steven A.

AU - O'Brien, William F.

AU - Spellacy, William N.

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N2 - 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 Ca2+ 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.

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

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