Endocrinology and Diabetes Clinic, University Hospital of Heraklion, School of Medicine, University of Crete, 71500 Crete, Greece.
Medicina (Kaunas). 2023 Apr 21;59(4):812. doi: 10.3390/medicina59040812.
Pituitary neuroendocrine tumors (PitNETs), the third most common intracranial tumor, are mostly benign. However, some of them may display a more aggressive behavior, invading into the surrounding structures. While they may rarely metastasize, they may resist different treatment modalities. Several major advances in molecular biology in the past few years led to the discovery of the possible mechanisms involved in pituitary tumorigenesis with a possible therapeutic implication. The mutations in the different proteins involved in the Gsa/protein kinase A/c AMP signaling pathway are well-known and are responsible for many PitNETS, such as somatotropinomas and, in the context of syndromes, as the McCune-Albright syndrome, Carney complex, familiar isolated pituitary adenoma (FIPA), and X-linked acrogigantism (XLAG). The other pathways involved are the MAPK/ERK, PI3K/Akt, Wnt, and the most recently studied HIPPO pathways. Moreover, the mutations in several other tumor suppressor genes, such as and , are responsible for the MEN1 and MEN4 syndromes and succinate dehydrogenase (SDHx) in the context of the 3PAs syndrome. Furthermore, the pituitary stem cells and miRNAs hold an essential role in pituitary tumorigenesis and may represent new molecular targets for their diagnosis and treatment. This review aims to summarize the different cell signaling pathways and genes involved in pituitary tumorigenesis in an attempt to clarify their implications for diagnosis and management.
垂体神经内分泌肿瘤（PitNETs）是第三常见的颅内肿瘤，大多为良性。然而，其中一些可能表现出更具侵袭性的行为，侵犯周围结构。尽管它们很少转移，但可能对不同的治疗方式产生抵抗。过去几年分子生物学的几项重大进展导致发现了可能涉及垂体肿瘤发生的潜在机制，并具有可能的治疗意义。涉及 Gsa/蛋白激酶 A/cAMP 信号通路的不同蛋白的突变是众所周知的，它们与许多 PitNETs 有关，如生长激素瘤，并且在综合征的背景下，如 McCune-Albright 综合征、Carney 综合征、家族性孤立性垂体腺瘤（FIPA）和 X 连锁肢端巨大症（XLAG）。涉及的其他途径是 MAPK/ERK、PI3K/Akt、Wnt，以及最近研究的 HIPPO 途径。此外，几种其他肿瘤抑制基因的突变，如 和 ，与 MEN1 和 MEN4 综合征以及 3PAs 综合征中的琥珀酸脱氢酶（SDHx）有关。此外，垂体干细胞和 miRNAs 在垂体肿瘤发生中起着至关重要的作用，可能成为其诊断和治疗的新分子靶点。本综述旨在总结涉及垂体肿瘤发生的不同细胞信号通路和基因，试图阐明它们对诊断和管理的意义。
