New potential regulators of uterine leiomyomata from DNA arrays: the ionotropic glutamate receptor GluR2.
New potential regulators of uterine leiomyomata from DNA arrays: the ionotropic glutamate receptor GluR2.
复制标题
DNA 阵列中子宫肌瘤的新潜在调节因子：离子型谷氨酸受体 GluR2。
DOI：
10.1016/j.bbrc.2003.09.189
复制
发表时间：
2003
影响因子：
3.1
通讯作者：
Spellacy,WilliamN
中科院分区：
文献类型：
--
作者：
Tsibris,JohnCM;Maas,Stefan;Segars,JamesH;Nicosia,SantoV;Enkemann,StevenA;O'Brien,WilliamF;Spellacy,WilliamN
在后基因组时代，子宫肌瘤的生长调控出现了新的概念。用DNA芯片筛选平滑肌瘤和子宫肌层组织，发现许多在平滑肌瘤中上调的基因在人类子宫中不表达。GluR 2是配体门控阳离子通道的一个亚基，在蛋白质和mRNA水平上在平滑肌瘤中相对于子宫肌层上调15- 30倍，并定位于内皮细胞。在平滑肌瘤和子宫肌层组织中，GluR 2前mRNA在Q/R位点几乎100%编辑，表明离子通道的低Ca 2+渗透性。在女性自发性平滑肌瘤或豚鼠模型中诱导的平滑肌瘤中，雌二醇和全反式维甲酸的产生增加与核受体PPARγ和RXRα蛋白的上调可能存在协同作用，以支持肿瘤生长。GluR 2可能与这种协同作用直接偶联，或通过在平滑肌瘤中上调的白细胞介素-17 B、驱动蛋白KIF 5或相关基因偶联。GluR拮抗剂应作为平滑肌瘤生长抑制剂进行试验。
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.