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Mol Cell Endocrinol. 2015 Dec 5;417:73-83. doi: 10.1016/j.mce.2015.09.016. Epub 2015 Sep 21.

Differential somatostatin receptor (SSTR) 1-5 expression and downstream effectors in histologic subtypes of growth hormone pituitary tumors.

Author information

1
Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Research Service Veterans Affairs Medical Center, Denver, CO 80220, USA. Electronic address: katja.kiseljak-vassiliades@ucdenver.edu.
2
Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
3
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
4
Division of Biostatistics and Bioinformatics, National Jewish Health, Denver, CO 80206, USA.
5
Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
6
Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
7
Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Research Service Veterans Affairs Medical Center, Denver, CO 80220, USA.

Abstract

PURPOSE:

The aim of this study was to examine whether differential expression of somatostatin receptors (SSTR) 1-5 and downstream effectors are different in densely (DG) and sparsely (SG) granulated histological growth hormone (GH) pituitary tumor subtypes.

METHODS:

The study included 33 acromegalic patients with 23 DG and 10 SG tumors. SSTR1-5 were measured by qPCR and immunoblotting. Signaling candidates downstream of SSTR2 were also assessed.

RESULTS:

SSTR2 mRNA and protein levels were significantly higher in DG compared to SG tumors. Downstream of SSTR2, p27(kip1) was decreased (2.6-fold) in SG compared to DG tumors, suggesting a potential mechanism of SSA resistance in SG tumors with intact SSTR2 expression. Re-expression of E-cadherin in GH pituitary cell increased p27(kip1) levels.

CONCLUSIONS:

Histological subtyping correlated with SSTR2, E cadherin and p27(kip) protein levels and these may serve as useful biomarkers in GH tumors to predict behavior and response to therapy with SSA.

KEYWORDS:

Acromegaly; Dense GH tumors; Somatostatin receptor; Sparse GH tumors

PMID:
26391562
PMCID:
PMC4641524
DOI:
10.1016/j.mce.2015.09.016
[Indexed for MEDLINE]
Free PMC Article

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