Document Detail


Insulin-like growth factor I stimulates telomerase activity in prostate cancer cells.
MedLine Citation:
PMID:  12843187     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
IGF-I has been implicated in the pathogenesis of human cancer. We sought to establish a role for IGF-I in the regulation of telomerase, an enzyme critically involved in cancer cell immortalization. Telomerase activity was assayed in LAPC-4, PC-3, and DU-145 prostate cancer cell lines treated with and without IGF-I/IGF-I analogs. Relative expression of human telomerase reverse transcriptase (hTERT) mRNA and protein was determined by quantitative RT-PCR and Western immunoblot, respectively. IGF-I stimulated baseline telomerase activity in all three cell lines, ranging from 2- to 10-fold (P < 0.05). Enhancement was noted at IGF concentrations as low as 10 ng/ml and was maximal at 100 ng/ml. Stimulation was noted by 0.5 h, was maximal by 8 h, and persisted to 48 h. A similar 3-fold enhancement (P < 0.01) was noted in response to Long-R3 IGF-I, but not in response to [Ala(31),Leu(60)]IGF-I. Pretreatment with the Akt kinase inhibitor wortmannin abolished the stimulatory IGF effect, whereas blockade of MAPK activity did not. Lastly, IGF-I provoked a 2-fold increase in hTERT mRNA and protein expression (P < 0.01). In summary, IGF-I clearly stimulates telomerase activity in prostate cancer cells through a dual mode of action, including early rapid effects probably involving phosphorylation of hTERT by Akt and later up-regulation of hTERT expression.
Authors:
Lawrence A Wetterau; Malik J Francis; Liqun Ma; Pinchas Cohen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  88     ISSN:  0021-972X     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2003 Jul 
Date Detail:
Created Date:  2003-07-04     Completed Date:  2003-08-08     Revised Date:  2012-06-22    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3354-9     Citation Subset:  AIM; IM    
Affiliation:
Columbus Children's Hospital, Ohio State University College of Medicine, Columbus, Ohio 43205, USA. lwetterau@chi.osu.edu
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MeSH Terms
Descriptor/Qualifier:
DNA-Binding Proteins
Dose-Response Relationship, Drug
Enzyme Activation / drug effects
Gene Expression Regulation, Enzymologic / drug effects
Humans
Insulin-Like Growth Factor I / pharmacology*
Male
Phosphatidylinositol 3-Kinases / metabolism
Phosphorylation
Prostatic Neoplasms*
Protein-Serine-Threonine Kinases*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
RNA, Messenger / analysis
Receptor, IGF Type 1 / metabolism
Telomerase / genetics,  metabolism*
Tumor Cells, Cultured / drug effects,  enzymology
Grant Support
ID/Acronym/Agency:
1R01-AI-40203/AI/NIAID NIH HHS; 2R01-DK-47591/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 67763-96-6/Insulin-Like Growth Factor I; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptor, IGF Type 1; EC 2.7.11.1/AKT1 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.7.49/Telomerase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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