FLNA expression modulates pathological markers of pituitary neuroendocrine tumours.

IF 3.4 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM Journal of Endocrinology Pub Date : 2023-11-22 Print Date: 2024-01-01 DOI:10.1530/JOE-23-0209
Jonathan Toledo, Pablo Aníbal Perez, Mical Zanetti, Graciela Díaz-Torga, Jorge Humberto Mukdsi, Silvina Gutierrez
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Abstract

Due to the current limited knowledge about the role of filamin A (FLNA) in pituitary tumour progression, we aimed to analyse FLNA expression levels and its impact on aggressive markers of pituitary neuroendocrine tumours (PitNETs), using an integrative approach of in vivo and in vitro models and human samples. An increase in the expression levels of FLNA was observed in the advanced tumoural stages of the hyperplastic adenomatous pituitary model, concomitant with a decrease in cell proliferation and with a modification in the subcellular localisation of this protein. Similarly, overexpression of FLNA in the somatolactotropic GH3 cell line induced a decrease in the cell proliferation, promoted a migratory phenotype, increased invasion activity, and decreased the prolactin secretion. Cyclin D1 (CCND1) and cyclin-dependent kinase 4 (CDK4) expression increased in both models in correlation with the increase observed in FLNA levels. When human tissues were analysed a significant increase of FLNA was observed in PitNETs compared to normal pituitary gland, with heterogeneous intracellular localisation. Higher levels of FLNA expression were observed in tumours with invasive characteristics. These results underline the crucial roles of FLNA as a modulator of pathological markers and as a potential prognostic marker in pituitary tumours.

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FLNA的表达调节垂体神经内分泌肿瘤的病理标志物。
由于目前对filamin A(FLNA)在垂体肿瘤进展中的作用知之甚少,我们旨在使用体内和体外模型以及人类样本的综合方法,分析FLNA的表达水平及其对垂体神经内分泌肿瘤侵袭性标志物(PitNETs)的影响。在增生性腺瘤性垂体模型的晚期肿瘤阶段观察到FLNA表达水平的增加,伴随着细胞增殖的减少和该蛋白亚细胞定位的改变。类似地,促体乳GH3细胞系中FLNA的过表达诱导细胞增殖减少,促进迁移表型,增加侵袭活性,并减少催乳素分泌。细胞周期蛋白D1(CCND1)和细胞周期蛋白依赖性激酶4(CDK4)在两种模型中的表达均增加,与FLNA水平的增加相关。当分析人类组织时,与正常垂体相比,在PitNETs中观察到FLNA的显著增加,具有异质性的细胞内定位。在具有侵袭性特征的肿瘤中观察到较高水平的FLNA表达。这些结果强调了FLNA作为病理标志物的调节剂和作为垂体肿瘤潜在预后标志物的关键作用。
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来源期刊
Journal of Endocrinology
Journal of Endocrinology 医学-内分泌学与代谢
CiteScore
7.90
自引率
2.50%
发文量
113
审稿时长
4-8 weeks
期刊介绍: Journal of Endocrinology is a leading global journal that publishes original research articles, reviews and science guidelines. Its focus is on endocrine physiology and metabolism, including hormone secretion; hormone action; biological effects. The journal publishes basic and translational studies at the organ, tissue and whole organism level.
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