Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary.
Expression of the pituitary stem/progenitor marker GFRα2 in human pituitary adenomas and normal pituitary.
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DOI：
10.1007/s11102-014-0553-1
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发表时间：
2015-02
期刊：
影响因子：
3.8
通讯作者：
Quinones-Hinojosa, Alfredo
中科院分区：
文献类型：
--
作者：
Mathioudakis, Nestoras;Sundaresh, Ram;Larsen, Alexandra;Ruff, William;Schiller, Jennifer;Guerrero-Cazares, Hugo;Burger, Peter;Salvatori, Roberto;Quinones-Hinojosa, Alfredo
关键词：
最近的研究表明，成体垂体干细胞可能在垂体肿瘤发生中发挥作用。我们试图探讨胶质细胞源性神经营养因子受体α 2（GFRα2），一种最近描述的垂体干/祖细胞标志物，是否可能在垂体腺瘤和正常垂体中差异表达。应用RT-PCR、Western blot和免疫组化方法检测39例垂体腺瘤、14例正常垂体和3例正常垂体cDNA中GFRα2和GFR受体家族其它成员（GFRα1、α3、α4）的表达。GFRα2 mRNA在功能性腺瘤中的表达是正常垂体的2.6倍（P <0.01），在非功能性腺瘤中的表达是正常垂体的3.5倍（P <0.05）。在NFA中，GFRα2仅在促性腺激素瘤亚型中显著过表达（~5倍）（P<0.05）。GFRα2蛋白表达在大多数NFA中似乎较高，尽管该组中蛋白表达存在异质性。免疫组化和蛋白质印迹显示GFRα2蛋白表达在功能性腺瘤中持续降低。在正常垂体中，GFRα2定位于Rathke残体、假定的垂体干细胞龛和促肾上腺皮质激素。我们的研究结果表明，垂体干细胞标志物GFRα2在功能性腺瘤中表达不足，而在NFA中过度表达，特别是促性腺激素瘤。GFRα2在促性腺激素瘤中的过度表达是否在垂体肿瘤发生中起作用还需要进一步研究。
Recent studies suggest that adult pituitary stem cells may play a role in pituitary tumorigenesis. We sought to explore whether the Glial cell-line derived neurotrophic factor receptor alpha 2 (GFRα2), a recently described pituitary stem/progenitor marker, might be differentially expressed in pituitary adenomas versus normal pituitary. The expression of GFRα2 and other members of the GFR receptor family (GFRα1, α3, α4) were analyzed using RT-PCR, western blot, and immunohistochemistry in 39 pituitary adenomas, 14 normal pituitary glands obtained at autopsy, and cDNA from 3 normal pituitaries obtained commercially. GFRα2 mRNA was ~2.6 fold under-expressed in functioning adenomas (P <0.01) and ~3.5 fold over-expressed in non-functioning adenomas (NFAs) (P <0.05) compared to normal pituitary. Among NFAs, GFRα2 was significantly over-expressed (~5-fold) in the gonadotropinoma subtype only (P<0.05). GFRα2 protein expression appeared to be higher in most NFAs, although there was heterogeneity in protein expression in this group. GFRα2 protein expression appeared consistently lower in functioning adenomas by IHC and western blot. In normal pituitary, GFRα2 was localized in Rathke’s remnant, the putative pituitary stem cell niche, and in corticotropes. Our results suggest that the pituitary stem cell marker GFRα2 is under-expressed in functioning adenomas and over-expressed in NFAs, specifically gonadotropinomas. Further studies are required to elucidate whether over-expression of GFRα2 in gonadotropinomas might play a role in pituitary tumorigenesis.
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影响因子：
7
作者：
Chen, GA;Gharib, TG;Beer, DG
通讯作者：
Beer, DG
影响因子：
3
作者：
Cooper, Odelia;Ben-Shlomo, Anat;Melmed, Shlomo
通讯作者：
Melmed, Shlomo
影响因子：
5.8
作者：
Japón, MA;Urbano, AG;Alvarez, CV
通讯作者：
Alvarez, CV
影响因子：
3.2
作者：
Nolan, L. A.;Levy, A.
通讯作者：
Levy, A.
DOI：
10.1186/1756-9966-29-39
发表时间：
2010-04-28
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Kordek R;Potemski P;Kusinska R;Pluciennik E;Bednarek A
通讯作者：
Bednarek A