TY - JOUR
T1 - Expression of the antiapoptotic gene seladin-1 and octreotide-induced apoptosis in growth hormone-secreting and nonfunctioning pituitary adenomas
AU - Luciani, Paola
AU - Gelmini, Stefania
AU - Ferrante, Emanuele
AU - Lania, Andrea
AU - Benvenuti, Susanna
AU - Baglioni, Silvana
AU - Mantovani, Giovanna
AU - Cellai, Ilaria
AU - Ammannati, Franco
AU - Spada, Anna
AU - Serio, Mario
AU - Peri, Alessandro
PY - 2005/11
Y1 - 2005/11
N2 - Context: Seladin-1 (from selective Alzheimer's disease indicator-1) is a recently discovered gene that has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 effectively protects neurons against β-amyloid-mediated toxicity and prevents apoptosis via inhibition of the activation of caspase-3, a key mediator of the apoptotic cascade. Although seladin-1 is expressed in the pituitary gland, no study addressed the expression or the function of this gene in pituitary adenomas. Objective: The aim of the present study was to determine the expression level of the seladin-1 gene in pituitary tumors, i.e. GH-secreting and nonfunctioning pituitary adenomas (NFPA), and to determine whether differential expression might be associated with different somatostatin (sst)-induced apoptosis. Results: We found by quantitative real-time RT-PCR that the expression level of seladin-1 was significantly higher in NFPA (n = 21) than in GH-secreting adenomas (n = 30; mean ± SE, 25.69 ± 6.39 vs. 8.02 ± 2.68 pg/μg total RNA; P = 0.006). Although the amount of activated caspase-3 did not differ between the two groups of tumors, in primary cell cultures, octreotide was able to increase apoptosis, evaluated by the level of cleaved cytokeratin 18 and the presence of apoptotic nuclei, in GH-secreting adenomas, but not in NFPA. This different response was not attributable to differences in the amount of transcript of sst receptors 2 and 5, which was similar in the two groups of tumors. Conclusions: Our results suggest that differential seladin-1 expression in pituitary adenomas may be associated with a different apoptotic response to sst analogs.
AB - Context: Seladin-1 (from selective Alzheimer's disease indicator-1) is a recently discovered gene that has been found to be down-regulated in brain regions affected by Alzheimer's disease. Seladin-1 effectively protects neurons against β-amyloid-mediated toxicity and prevents apoptosis via inhibition of the activation of caspase-3, a key mediator of the apoptotic cascade. Although seladin-1 is expressed in the pituitary gland, no study addressed the expression or the function of this gene in pituitary adenomas. Objective: The aim of the present study was to determine the expression level of the seladin-1 gene in pituitary tumors, i.e. GH-secreting and nonfunctioning pituitary adenomas (NFPA), and to determine whether differential expression might be associated with different somatostatin (sst)-induced apoptosis. Results: We found by quantitative real-time RT-PCR that the expression level of seladin-1 was significantly higher in NFPA (n = 21) than in GH-secreting adenomas (n = 30; mean ± SE, 25.69 ± 6.39 vs. 8.02 ± 2.68 pg/μg total RNA; P = 0.006). Although the amount of activated caspase-3 did not differ between the two groups of tumors, in primary cell cultures, octreotide was able to increase apoptosis, evaluated by the level of cleaved cytokeratin 18 and the presence of apoptotic nuclei, in GH-secreting adenomas, but not in NFPA. This different response was not attributable to differences in the amount of transcript of sst receptors 2 and 5, which was similar in the two groups of tumors. Conclusions: Our results suggest that differential seladin-1 expression in pituitary adenomas may be associated with a different apoptotic response to sst analogs.
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U2 - 10.1210/jc.2005-0633
DO - 10.1210/jc.2005-0633
M3 - Article
C2 - 16091489
AN - SCOPUS:27744470577
VL - 90
SP - 6156
EP - 6161
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 11
ER -