Activation of human somatostatin receptor type 2 causes inhibition of cell growth in transfected HEK293 but not in transfected CHO cells.
Somatostatin (SS) is known to have an antiproliferative effect on cell growth via somatostatin receptors (SSTR). The purpose of this study was to transfect cell lines with human SSTR2 and determine the subsequent effect on cell growth in response to SSTR agonist. Heterologous Chinese hamster ovary (CHO-K1) and human embryonic kidney 293 (HEK) cells were transfected with SSTR2 cDNA using lipofectin. Stable transformants were selected by G418 and confirmed by 125I-SS binding and RT-PCR. Binding studies were performed in the presence of 10(-6) to 10(-12) M SS-14, SS-28, SS analogue RC-160, SSTR2 agonist NC-9-74, and SSTR5 agonist DC-37-39. Cell growth was determined by counting cell numbers after 48 hr incubation in the presence of 10(-6) to 10(-12) M SSTR2 agonist NC-9-74. Binding of 125I-SS-14 to transfected CHO and transfected HEK293 cells showed that the cells had high affinity for SS-14, SS-28, NC-9-74, and RC-160 but low affinity for DC-37-39. Incubation with 10(-6) to 10(-12) M NC-9-74, showed that 1 nM to 1 microM NC-9-74 significantly inhibited transfected HEK293 cell growth but did not affect growth on transfected CHO cells (n = 4 for each dose, P < 0.01). The two cell lines transfected with the human SSTR2 showed similar high affinity for SS-14, SS-28, RC-160, and SSTR2 agonist but not SSTR5 agonist. The SSTR2 agonist NC-9-74 significantly inhibited transfected HEK293 cell growth but not CHO cells. These data suggest that activation of SSTR2 was more efficiently coupled to the signal transduction pathway of antiproliferation in the transfected HEK293 cells.
Ren
J
J
Department of Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
Bell
G
G
Coy
D H
DH
Brunicardi
F C
FC
D000818:Animals; D016466:CHO Cells / Q000502:physiology*; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D015870:Gene Expression; D006801:Humans; D007668:Kidney / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D017481:Receptors, Somatostatin / Q000819:agonists / Q000502:physiology*; D011994:Recombinant Proteins; D015398:Signal Transduction; D013004:Somatostatin / Q000378:metabolism*
D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; D013004:Somatostatin; C093733:somatostatin receptor 2