Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of somatostatin receptor subtypes 2 and 5 (SSTR2 and SSTR5) in determining the secretory and proliferative phenotype as well as the sensitivity to somatostatin analogue treatment is not clearly established. We quantified the expression of SSTR2 and SSTR5 mRNA using a semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in 19 human growth hormone (GH) -secreting adenomas. Tumour characteristics and in vivo sensitivity to somatostatin analogues were assessed; tumours were screened for Gsalpha gene mutations. PCR products of SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were directly sequenced. All tumours expressed both SSTR2 and SSTR5 mRNA at variable levels. No significant correlation between SSTR2 and SSTR5 expression and the presence of Gsalpha mutation, GH levels, or tumour size and invasiveness was observed. A negative correlation between SSTR2 and SSTR5 mRNA levels was observed (r = 0.5; P < 0.05). No significant correlation between the levels of SSTR2 and SSTR5 expression and the in vivo responsiveness to somatostatin analogues was observed, although a tendency to a low SSTR2 expression in resistant tumours was found. No mutations in the coding or bordering regions of either SSTR2 or SSTR5 adenomatous DNA from patients totally or partially resistant to somatostatin analogues were found. The study shows that the different expression of SSTR2 and SSTR5 in GH-secreting adenomas is not significantly correlated with the secretory and proliferative phenotype, although the large, hypersecretory tumours and those with a poor sensitivity to somatostatin analogues seem to express low levels of SSTR2 mRNA. Moreover, both SSTR2 and SSTR5 DNA from tumours resistant to somatostatin analogues were found to possess intact coding sequences.
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PMID:Somatostatin receptor subtype 2 and 5 in human GH-secreting pituitary adenomas: analysis of gene sequence and mRNA expression. 1126 47

Introduction of somatostatin analogs has greatly contributed to improving the prognosis of acromegaly. Although the majority of patients are effectively treated by these agents, resistance occurs in a subset of patients. So far, resistance to somatostatin has never been associated with mutations of the somatostatin receptor subtypes (sst2 and sst5) that inhibit GH secretion. Molecular analysis of genomic DNA from pituitary tumor and peripheral blood obtained from an acromegalic resistant to octreotide showed a somatic activating mutation of Gsalpha (Arg201Cys), no mutation in sst2, and one polymorphism (Pro109Ser) and one germ line mutation (Arg240Trp) in sst5. Wild-type (WT) and mutant sst5 PCR products were cloned and transfected into Chinese hamster ovary K1 cells. In Chinese hamster ovary K1 cells stably expressing mutant sst5, somatostatin-28 was less potent in inhibiting cyclic AMP levels than in WT cells. Proliferation of mutant cells exceeded that of WT by 50%. Moreover, somatostatin reduced cell growth and MAPK activity in WT but not in mutant cells in which the peptide even increased MAPK activity. We suggest that this mutation that abrogates the antiproliferative action of somatostatin and activates mitogenic pathways may be involved in the resistance to somatostatin treatment.
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PMID:Mutation of somatostatin receptor type 5 in an acromegalic patient resistant to somatostatin analog treatment. 1150 16

In recent years the demonstration that human pituitary adenomas are monoclonal in origin has provided further evidence that pituitary neoplasia arise from the replication of a single mutated cell in which growth advantage results from either activation of proto-oncogenes or inactivation of tumor suppressor genes. While common oncogenes, such as Ras, are only exceptionally involved, the only mutations identified in a significant proportion of pituitary tumors, and particular in GH-secreting adenomas, occur in the Gsalpha gene (GNAS1) and cause constitutive activation of the cAMP pathway (gsp oncogene). Moreover, pituitary tumors overexpress hypothalamic releasing hormones, growth factors, and their receptors as well as cyclins involved in cell cycle progression. As far as the role of tumor suppressor genes in pituitary tumorigenesis is concerned, reduced expression of these genes seems to frequently occur in pituitary tumors as a consequence of abnormal methylation processes. Although the only mutational change so far identified in pituitary tumors is the gsp oncogene, this oncogene is not associated with a clear phenotype in patients bearing positive tumors. Mechanisms able to counteract the cAMP pathway, such as high sensitivity to somatostatin, and induction of genes with opposite actions, such as phosphodiesterases, CREB end ICER, or instability of mutant Gsalpha, have been proposed to account for the lack of genotype/phenotype relationships.
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PMID:Genetics of pituitary tumors: Focus on G-protein mutations. 1453 May 8