Activation of human somatostatin receptor 2 promotes apoptosis through a mechanism that is independent from induction of p53.
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.
Teijeiro
Rosa
R
Departamento de Fisioloxía, Facultade de Medicina, Universidade de Santiago de Compostela, Rua San Francisco s/n, 15705 Santiago de Compostela, Spain.
Rios
Ramón
R
Costoya
José A
JA
Castro
Ramón
R
Bello
José L
JL
Devesa
Jesús
J
Arce
Victor M
VM
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
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