Document Detail

Subtype-selective induction of wild-type p53 and apoptosis, but not cell cycle arrest, by human somatostatin receptor 3.
MedLine Citation:
PMID:  8961277     Owner:  NLM     Status:  MEDLINE    
Somatostatin (SST) exerts direct antiproliferative effects in tumor cells, triggering either growth arrest or apoptosis. The cellular actions of SST are transduced through a family of five distinct somatostatin receptor subtypes (SSTR1-5). Whereas growth inhibition has been reported to follow stimulation of protein tyrosine phosphatase via SSTR2 or inhibition of Ca2+ channels via SSTR5 in heterologous expression systems, the subtype selectivity for signaling apoptosis has not been investigated. The tumor suppressor protein p53 and the protooncogene product c-Myc regulate cell cycle progression (growth factors present) or apoptosis (growth factors absent). The p53-induced G1 arrest requires induction of p21, an inhibitor of cyclin-dependent kinases, whereas apoptosis requires induction of Bax. c-Myc is capable of abrogating p53-induced G1 arrest by interfering with the inhibitory action of p21 on cyclin-dependent kinases. We have, therefore, investigated the regulation of p53, p21, c-Myc, and Bax and cellular apoptosis in relation to cell cycle progression in CHO-K1 cells stably expressing individual human SSTR1-5. We demonstrate that apoptosis is signaled uniquely through human SSTR3 and is associated with dephosphorylation-dependent conformational change in wild-type (wt) p53 as well as induction of Bax. The induction of wt p53 occurs rapidly and precedes the onset of apoptosis. We show that the increase in wt p53 is not associated with the induction of p21 or c-Myc when octreotide-induced apoptosis becomes evident, suggesting that such apoptosis does not require G1 arrest and is not c-Myc dependent. These findings provide the first evidence for hormonal induction of wt p53-associated apoptosis via G protein-coupled receptor in a subtype-selective manner.
K Sharma; Y C Patel; C B Srikant
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  10     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1996 Dec 
Date Detail:
Created Date:  1997-03-20     Completed Date:  1997-03-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1688-96     Citation Subset:  IM    
Fraser Laboratories for Diabetes Research McGill University and Royal Victoria Hospital Montreal, Quebec, Canada.
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MeSH Terms
Antineoplastic Agents, Hormonal / pharmacology
Apoptosis / drug effects,  physiology*
CHO Cells / drug effects,  metabolism
Cell Cycle / drug effects,  physiology*
Cyclin-Dependent Kinase Inhibitor p21
Cyclins / drug effects,  genetics,  metabolism
GTP-Binding Proteins / drug effects,  metabolism
Gene Expression Regulation, Neoplastic
Octreotide / pharmacology
Proto-Oncogene Proteins / drug effects,  genetics,  metabolism
Proto-Oncogene Proteins c-bcl-2*
Proto-Oncogene Proteins c-myc / drug effects,  genetics,  metabolism
Receptors, Somatostatin / genetics,  metabolism*
Signal Transduction
Tumor Suppressor Protein p53 / drug effects,  genetics,  metabolism*
bcl-2-Associated X Protein
Reg. No./Substance:
0/Antineoplastic Agents, Hormonal; 0/BAX protein, human; 0/CDKN1A protein, human; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Hormones; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Proto-Oncogene Proteins c-myc; 0/Receptors, Somatostatin; 0/Tumor Suppressor Protein p53; 0/bcl-2-Associated X Protein; 0/somatostatin receptor 3; 0/somatostatin receptor 5; 83150-76-9/Octreotide; EC 3.6.1.-/GTP-Binding Proteins

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