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

Katja Kiseljak-Vassiliades; Mei Xu; Taylor S Mills; Elizabeth E Smith; Lori J Silveira; Kevin O Lillehei; Janice M Kerr; B K Kleinschmidt-DeMasters; Margaret E Wierman

doi:10.1016/j.mce.2015.09.016

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

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

Authors

Katja Kiseljak-Vassiliades¹, Mei Xu², Taylor S Mills², Elizabeth E Smith³, Lori J Silveira⁴, Kevin O Lillehei⁵, Janice M Kerr², B K Kleinschmidt-DeMasters⁶, Margaret E Wierman⁷

Affiliations

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adult
Biomarkers, Tumor / genetics
Biomarkers, Tumor / metabolism
Cadherins / genetics
Cadherins / metabolism*
Cell Line, Tumor
Cyclin-Dependent Kinase Inhibitor p27 / genetics
Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Middle Aged
Pituitary Neoplasms / genetics*
Pituitary Neoplasms / metabolism
Pituitary Neoplasms / pathology*
Receptors, Somatostatin / genetics*
Receptors, Somatostatin / metabolism*
Retrospective Studies
Signal Transduction

Substances

Biomarkers, Tumor
CDKN1B protein, human
Cadherins
Receptors, Somatostatin
SSTR2 protein, human
Cyclin-Dependent Kinase Inhibitor p27

Abstract

Publication types

MeSH terms

Substances

Grants and funding