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. 2013 Jun;68(6):887-91.
doi: 10.6061/clinics/2013(06)26.

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

Ricardo V Araujo  1 , Claudia V Chang, Valter A S Cescato, Maria Candida B V Fragoso, Marcello D Bronstein, Berenice B Mendonca, Ivo J P Arnhold, Luciani R S Carvalho
Affiliations

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

Ricardo V Araujo et al. Clinics (Sao Paulo). 2013 Jun.

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.

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Conflict of interest statement

No potential conflict of interest was reported.

Figures

Figure 1
Figure 1
Transcriptional profile of PROP1 and POU1F1 in pituitary adenomas. Analysis of the RT-qPCR array showed that PROP1 expression was 18-fold higher in the corticotrophinomas, 10-fold higher in the somatotrophinomas, and 3-fold higher in the nonfunctioning adenomas. POU1F1 was overexpressed only in the somatotrophinomas (3-fold increase). The results are expressed as the means ± SD of quadruplicate assays. *p<0.025. ACTH_PA, ACTH-producing adenomas; GH_PA, GH-producing adenomas; NF_A, nonfunctioning adenomas.
Figure 2
Figure 2
Transcriptional profile of hormone-producing genes in pituitary adenomas. POMC expression was 65-fold higher in the corticotrophinomas. GH was constitutively expressed in almost all of the somatotrophinoma samples analyzed. The expression of hormone-producing genes was downregulated in the nonfunctioning adenomas. The results are expressed as the means ± SD of quadruplicate assays.
Figure 3
Figure 3
Transcriptional profile of TBX19 in pituitary adenomas. RT-qPCR analyses showed that TBX19 expression was 27-fold higher in the corticotrophinomas. The results are expressed as the means ± SD of quadruplicate assays. *p<0.025. ACTH_PA, ACTH-producing adenomas; GH_PA, GH-producing adenomas; NF_A, nonfunctioning adenomas.
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