title: Human somatostatin receptor-3 distinctively induces apoptosis in MCF-7 and cell cycle arrest in MDA-MB-231 breast cancer cells.
abstract: Somatostatin (SST) mediates cytostatic and pro-apoptotic effects through five somatostatin receptors (SSTR1-5). The modest clinical benefits of SST analogs in cancers of different origin such as breast cancer are attributed to diminished SSTRs expression at tumor sites. In the present study, SSTR3 was overexpressed in MCF-7 and MDA-MB-231, and analyzed for downstream signaling molecules associated with cytostatic and cytotoxic effect. Cells overexpressing SSTR3 displayed inhibition of EGF induced proliferation and enhanced antiproliferative effect of SSTR3-specific agonist in comparison to non-transfected cells. SSTR3 overexpression in MCF-7 cells (R3-MCF-7) constitutively enhanced TUNEL staining, PARP-1 and p27(Kip1) expression suggesting apoptosis and cell-cycle arrest. Conversely, R3-MB-231 cells with SSTR3 overexpression exerted cytostatic and were devoid of any cytotoxic effects. The expression of PTP-1C and the status of ERK1/2, p38 and PI3K phosphorylation was modulated in a cell-specific manner. These findings provide new insights in understanding the antiproliferative role of SSTR3 in breast tumor biology.
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Sajad A
authors.initials: SA
authors.lastname: War
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Brian
authors.initials: B
authors.lastname: Kim
authors.affiliation: Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada. Electronic address: ujkumar@mail.ubc.ca.
authors.forename: Ujendra
authors.initials: U
authors.lastname: Kumar
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D059447:Cell Cycle Checkpoints; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System; D061986:MCF-7 Cells; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: C436291:CDKN1B protein, human; D009363:Neoplasm Proteins; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; D050760:Cyclin-Dependent Kinase Inhibitor p27; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D019869:Phosphatidylinositol 3-Kinases; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Apoptosis; Breast cancer; G protein-coupled receptor; Somatostatin; Somatostatin receptor-3