PROP1 overexpression in corticotrophinomas: evidence for the role of PROP1 in the maintenance of cells committed to corticotrophic differentiation

Abstract

OBJECTIVE:The expression of transcription factors involved in early pituitary development, such as PROP1 and POU1F1, has been detected in pituitary adenoma tissues. In this study, we sought to characterize the transcriptional profiles of PROP1, POU1F1, and TBX19 in functioning and nonfunctioning pituitary adenomas in an attempt to identify their roles in tumorigenesis and hormone hypersecretion.METHODS:RT-qPCR analyses were performed to assess the transcriptional pattern of PROP1, POU1F1, TBX19, and hormone-producing genes in tissue samples of corticotrophinomas (n = 10), somatotrophinomas (n = 8), and nonfunctioning adenomas (n = 6).RESULTS:Compared with normal pituitary tissue, POU1F1 was overexpressed in somatotrophinomas by 3-fold. PROP1 expression was 18-fold higher in corticotrophinomas, 10-fold higher in somatotrophinomas, and 3-fold higher in nonfunctioning adenomas. TBX19 expression was 27-fold higher in corticotrophinomas. Additionally, the level of TBX19 mRNA positively correlated with that of pro-opiomelanocortin (r = 0.49, p = 0.014).CONCLUSIONS:Our data demonstrate that PROP1 is overexpressed in pituitary adenomas, mainly in corticotrophinomas. Together with previously published data showing that patients who harbor PROP1 loss-of-function mutations present a progressive decline in corticotrope function, our results support a role for PROP1 in pituitary tumor development and in the maintenance of cell lineages committed to corticotrophic differentiation.

Genetic Approaches to Hypothalamic-Pituitary-Adrenal Axis Regulation

“…Another transcription factor, Prophet of Pit-1 gene (POMC) encodes a paired-like homeodomain protein and is expressed early in pituitary gland development and regulates cell differentiation (Araujo et al, 2013;Raetzman et al, 2004). Patients with pituitary corticotroph tumors express high levels of PROP1, which leads to increased expression of POMC and ACTH (Araujo et al, 2013).…”

Detection of insertion/deletions (indels) of the <i>ATBF1</i> gene and their effects on growth-related traits in three indigenous goat breeds

“…The AT motif-binding factor (ATBF1), also known as zinc finger homeobox 3 (ZFHX3), is a crucial cancer suppressor gene. It is worth mentioning that ATBF1 could promote the expression levels of the growth hormone prolactin and TSH-β by binding to the enhancers of POU1F1 (also known as Pit1) and PROP1 (Darling et al, 1998;Qi et al, 2008;Araujo et al, 2013;Yan et al, 2018). These studies showed that the ATBF1 gene was hypothesized to produce important effects on cell differentiation and early development, suggesting that the ATBF1 gene would affect the growth traits in animals.…”

Evaluation of novel SNPs and haplotypes within the <i>ATBF1</i> gene and their effects on economically important production traits in cattle

“…Furthermore, ATBF1 could promote the expression level of the growth hormone 1 (GH1) gene by binding to the enhancers of the POU1F1 and PROP1 genes (Araujo et al, 2013;Qi et al, 2008), which are the key genes in mammalian growth, development and the lactationrelated hypothalamic-pituitary-adrenal (HPA) axis pathway (PITX2/PITX1 -HESX1 -LHX3/LHX4 -PROP1 -POU1F1) (Davis et al, 2010;Ma et al, 2017). In addition, another key gene in the HPA axis pathway, PITX2, has a positive regulation relationship with ATBF1 under the participation of miR-1 (Huang et al, 2015).…”