Expression of the antiapoptotic gene seladin-1 and octreotide-induced apoptosis in growth hormone-secreting and nonfunctioning pituitary adenomas.
BACKGROUND
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 beta-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/microg 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.
Luciani
Paola
P
Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Gelmini
Stefania
S
Ferrante
Emanuele
E
Lania
Andrea
A
Benvenuti
Susanna
S
Baglioni
Silvana
S
Mantovani
Giovanna
G
Cellai
Ilaria
I
Ammannati
Franco
F
Spada
Anna
A
Serio
Mario
M
Peri
Alessandro
A
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015282:Octreotide / Q000494:pharmacology*; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000235:genetics
D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D019382:Human Growth Hormone; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D015282:Octreotide