Impact of gsp oncogene on the mRNA content for somatostatin and dopamine receptors in human somatotropinomas.

Abstract

INTRODUCTION:

It has been reported in some series that gsp+ somatotropinomas are more sensitive to somatostatin analogues (SA) and dopamine's actions which may be related to their somatostatin receptor (SSTR) and dopamine receptor (DR) profile. No previous studies have been undertaken to evaluate the SSTR and DR profile related with the gsp status in somatotropinomas.

OBJECTIVES:

To determine if (1) gsp status is correlated with response to octreotide LAR (LAR) and tumor expression patterns of SSTR1-5 and DR1-5 and (2) cAMP level can directly modulate SSTR and DR mRNA levels.

METHODS:

Response to SA was evaluated by GH and IGF-I percent reduction after 3 and 6 months of treatment with LAR. Conventional PCR and sequencing were used to identify gsp+ tumors. Quantitative real-time PCR was used to determine SSTR and DR tumor expression. Primary pituitary cell cultures of primates were used to study whether SSTR and DR expression is regulated by forskolin.

RESULTS:

The response to LAR did not significantly differ between patients with gsp+ and gsp- tumors; however, gsp+ tumors expressed higher levels of SSTR1, SSTR2, DR2 and a lower level of SSTR3. Forskolin increased SSTR1, SSTR2, DR1 and DR2 expression in cell cultures.

CONCLUSION:

Elevated SSTR1, SSTR2, and DR2 tumor expression may help improve responsiveness to SA and DA therapy; however, this study may not have been appropriately powered to observe significant effects in the clinical response. Elevated cAMP levels could be directly responsible for the upregulation in SSTR1, SSTR2 and DR2 mRNA levels observed in gsp+ patients.

• Authors: Giselle Fernandes Taboada, Leonardo Vieira Neto, Raul M Luque, Jose Córdoba-Chacón, Evelyn de Oliveira Machado, Denise Pires de Carvalho, Rhonda D Kineman, Mônica Roberto Gadelha
• Journal: Neuroendocrinology (Neuroendocrinology) Vol. 93 Issue 1 Pg. 40-7 ( 2011) ISSN: 1423-0194 [Electronic] Switzerland
• PMID: 21079388 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 S. Karger AG, Basel.

Chemical References

• Biomarkers, Pharmacological
• Chromogranins
• Delayed-Action Preparations
• Receptors, Dopamine
• Receptors, Somatostatin
• Colforsin
• GNAS protein, human
• GTP-Binding Protein alpha Subunits, Gs
• Octreotide

Topics

• Adenoma (blood, drug therapy, metabolism)
• Adolescent
• Adult
• Animals
• Biomarkers, Pharmacological (blood)
• Cell Culture Techniques
• Chromogranins
• Colforsin (pharmacology)
• Delayed-Action Preparations
• Female
• GTP-Binding Protein alpha Subunits, Gs (metabolism)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Male
• Middle Aged
• Octreotide (administration & dosage, pharmacology)
• Papio anubis
• Pituitary Gland (drug effects, metabolism)
• Pituitary Neoplasms (blood, drug therapy, metabolism)
• Receptors, Dopamine (biosynthesis)
• Receptors, Somatostatin (biosynthesis)