Expression of the Antiapoptotic Gene Seladin-1 and Octreotide-Induced Apoptosis in Growth Hormone-Secreting and Nonfunctioning Pituitary Adenomas
Paola Luciani,
Stefania Gelmini,
Emanuele Ferrante,
Andrea Lania,
Susanna Benvenuti,
Silvana Baglioni,
Giovanna Mantovani,
Ilaria Cellai,
Franco Ammannati,
Anna Spada,
Mario Serio and
Alessandro Peri
Endocrine Unit (P.L., S.Be., S.Ba., I.C., M.S., A.P.) and Clinical Biochemistry Unit (S.G.), Department of Clinical Physiopathology, Center for Research, Transfer, and High Education on Chronic, Inflammatory, Degenerative, and Neoplastic Disorders (DENOthe), University of Florence, 50139 Florence, Italy; Neurosurgery Unit, Careggi Hospital (F.A.), 50139 Florence, Italy; and Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore IRCCS (E.F., A.L., G.M., A.S.), 20122 Milan, Italy
Address all correspondence and requests for reprints to: Prof. Alessandro Peri, Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. E-mail: a.peri{at}dfc.unifi.it.
Context:Seladin-1 (from selective Alzheimer’s diseaseindicator-1) is a recently discovered gene that has been foundto be down-regulated in brain regions affected by Alzheimer’sdisease. Seladin-1 effectively protects neurons against ß-amyloid-mediatedtoxicity and prevents apoptosis via inhibition of the activationof caspase-3, a key mediator of the apoptotic cascade. Althoughseladin-1 is expressed in the pituitary gland, no study addressedthe expression or the function of this gene in pituitary adenomas.
Objective: The aim of the present study was to determine theexpression 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 associatedwith different somatostatin (sst)-induced apoptosis.
Results: We found by quantitative real-time RT-PCR that theexpression 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 totalRNA; P = 0.006). Although the amount of activated caspase-3did not differ between the two groups of tumors, in primarycell cultures, octreotide was able to increase apoptosis, evaluatedby the level of cleaved cytokeratin 18 and the presence of apoptoticnuclei, in GH-secreting adenomas, but not in NFPA. This differentresponse was not attributable to differences in the amount oftranscript of sst receptors 2 and 5, which was similar in thetwo groups of tumors.
Conclusions: Our results suggest that differential seladin-1expression in pituitary adenomas may be associated with a differentapoptotic response to sst analogs.
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