Expression of somatostatin receptor mRNA in human meningiomas and their implication in in vitro antiproliferative activity.
Somatostatin receptors (SSTRs) have been detected in many normal and malignant tissues. This wide expression has been used for diagnostic, prognostic and therapeutic purposes. Five SSTR subtypes (SSTR 1-5) have been identified whose activation is responsible for the signal transduction through many different intracellular pathways. In the present study the expression of SSTR mRNA was determined by reverse-transcriptase (RT)-PCR in 42 meningiomas. About 88% of the tumors analyzed (37/42) were positive for at least one of the five SSTR subtypes displaying a variable pattern of expression of the different SSTR subtypes. SSTRI and SSTR2 were the most frequently mRNA detected (69% and 79% of the sample analyzed, respectively). The other subtypes were found in the 43%, 33% and 33% of cases for SSTR3, SSTR4 and SSTR5, respectively. In 22, out of 42 patients (52%) three or more SSTRs were detected. The expression of the different SSTR subtypes did not correlate with the expression of bcl-2 (apoptosis-associated protein) and MIB-1 (a proliferation marker), assessed by immunohistochemistry in a series of 34 tumor samples, while a correlation between the expression of SSTR3 and p53 was observed (p = 0.08). To evaluate a possible role of SSTR in the control of human meningioma cell proliferation, seven primary cell cultures obtained from fresh meningioma surgical tissues, were analyzed for their proliferative behavior by MTT assay and for their response to SST by [3H]-thymidine incorporation. In four out of six tumors (in one case no SSTR were detected) the treatment with SST caused a significant inhibition of DNA synthesis induced by the tumor-promoter phorbol myristate acetate. The evidence of the expression of SSTRs, mainly of SSTR2, in this series of specimens we analyzed altogether with in vitro antiproliferative effects of SST may open interesting perspectives for the diagnosis and the therapy of meningiomas.
Arena
Sara
S
Section of Pharmacology, Department of Oncology, Biology and Genetics, Genetics, University of Genova, Italy.
Barbieri
Federica
F
Thellung
Stefano
S
Pirani
Paolo
P
Corsaro
Alessandro
A
Villa
Valentina
V
Dadati
Patrizia
P
Dorcaratto
Alessandra
A
Lapertosa
Gabriella
G
Ravetti
Jean-Louis
JL
Spaziante
Renato
R
Schettini
Gennaro
G
Florio
Tullio
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008577:Meningeal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008579:Meningioma / Q000378:metabolism* / Q000473:pathology*; D008875:Middle Aged; D020033:Protein Isoforms / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D019394:Ki-67 Antigen; D020033:Protein Isoforms; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D016159:Tumor Suppressor Protein p53