title: Activation of human somatostatin receptor 2 promotes apoptosis through a mechanism that is independent from induction of p53.
abstract: The ability of both somatostatin (SS) and its stable analogues to inhibit cell growth depends on the stimulation of specific membrane receptors (SSTR1-5), which belong to the G protein-coupled receptor family. Accumulating evidence suggests that the SSTR2 plays a major role in mediating cell cycle arrest, and it is also clear that SHP-1, a cytoplasmic phosphotyrosine phosphatase (PTP), is an essential component of the SSTR2-mediated cytostatic effect. In contrast, the possibility that SSTR2 activation may also lead to increased apoptosis is still beyond debate, despite SHP-1 activation is also able to promote cell death in several cell types. In the present work we have investigated the ability of SSTR2 to induce apoptosis in HL-60 cells. We have found that HL-60 cells uniquely express the SSTR2 subtype, and that stimulation of SSTR2 with the SS analogue SMS 201-995 results in an increased cell death. In all, these findings demonstrate that activation of SSTR2 promotes apoptosis in HL-60 cells. Moreover, in contrast with the proapoptotic mechanism previously reported for SSTR3, cell death induced by activation of SSTR2 is independent from accumulation of p53.
authors.affiliation: Departamento de Fisioloxía, Facultade de Medicina, Universidade de Santiago de Compostela, Rua San Francisco s/n, 15705 Santiago de Compostela, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Teijeiro
authors.forename: Ramón
authors.initials: R
authors.lastname: Rios
authors.forename: José A
authors.initials: JA
authors.lastname: Costoya
authors.forename: Ramón
authors.initials: R
authors.lastname: Castro
authors.forename: José L
authors.initials: JL
authors.lastname: Bello
authors.forename: Jesús
authors.initials: J
authors.lastname: Devesa
authors.forename: Victor M
authors.initials: VM
authors.lastname: Arce
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D016147:Genes, Tumor Suppressor; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D017481:Receptors, Somatostatin; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C093733:somatostatin receptor 2; D015282:Octreotide