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. 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.
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 acromegalicpatients 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.
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