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核心干细胞基因、和在人甲状旁腺肿瘤中表达,并受、和β-连环蛋白信号通路激活的调节。

The Core Stem Genes , , and Are Expressed in Human Parathyroid Tumors and Modulated by , , and β-catenin Pathways Activation.

作者信息

Verdelli Chiara, Morotti Annamaria, Tavanti Giulia Stefania, Silipigni Rosamaria, Guerneri Silvana, Ferrero Stefano, Vicentini Leonardo, Vaira Valentina, Corbetta Sabrina

机构信息

Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, 20161 Milan, Italy.

Department of Pathophysiology and Organ Transplantation, University of Milan, 20122 Milan, Italy.

出版信息

Biomedicines. 2021 Jun 2;9(6):637. doi: 10.3390/biomedicines9060637.

Abstract

Tumors of the parathyroid glands are the second most common endocrine neoplasia. Epigenetic studies revealed an embryonic signature involved in parathyroid tumorigenesis. Here, we investigated the expression of the stem core genes and . Rare cells within normal parathyroid glands expressed and , while was undetectable. Nuclear expression was detectable in 18% of parathyroid adenomas (PAds, = 34) involving 5-30% of cells, while and were expressed at the nuclear level in a more consistent subset of PAds involving 15-40% of cells. Most parathyroid carcinomas expressed the core stem genes. -expressing cells co-expressed parathormone (PTH). In PAds-derived primary cultures, silencing of the tumor suppressor gene induced the expression of , likely through a axis, while calcium-sensing receptor activation increased mRNA levels through activation. In addition, inducing nuclear β-catenin accumulation in PAds-derived primary cultures by short-term incubation with lithium chloride (LiCl), and expression levels increased, while transcripts were reduced, and LiCl long-term incubation induced an opposite pattern of gene expression. In conclusion, detection of the core stem genes in parathyroid tumors supports their embryogenic signature, which is modulated by crucial genes involved in parathyroid tumorigenesis.

摘要

甲状旁腺肿瘤是第二常见的内分泌肿瘤。表观遗传学研究揭示了一种参与甲状旁腺肿瘤发生的胚胎特征。在此,我们研究了干细胞核心基因[具体基因1]和[具体基因2]的表达。正常甲状旁腺内的罕见细胞表达[具体基因1]和[具体基因2],而[具体基因3]未检测到。在18%的甲状旁腺腺瘤(PAds,n = 34)中可检测到核[具体基因1]表达,涉及5%-30%的细胞,而[具体基因2]和[具体基因3]在15%-40%细胞的更一致的PAds亚组中在核水平表达。大多数甲状旁腺癌表达核心干细胞基因。表达[具体基因1]的细胞共表达甲状旁腺激素(PTH)。在源自PAds的原代培养物中,肿瘤抑制基因[具体基因4]的沉默可能通过[具体信号轴]诱导[具体基因1]的表达,而钙敏感受体激活通过[具体信号分子]激活增加[具体基因1]的mRNA水平。此外,通过与氯化锂(LiCl)短期孵育在源自PAds的原代培养物中诱导核β-连环蛋白积累,[具体基因1]和[具体基因2]的表达水平增加,而[具体基因3]转录本减少,LiCl长期孵育诱导相反的基因表达模式。总之,在甲状旁腺肿瘤中检测到核心干细胞基因支持它们的胚胎特征,这受到参与甲状旁腺肿瘤发生的关键基因的调节。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b3f/8227846/9a920e8db8cf/biomedicines-09-00637-g001.jpg

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