Insulin-like growth factor I stimulates telomerase activity in prostate cancer cells.
IGF-I significantly stimulates telomerase activity in prostate cancer cells, but these findings are based on in vitro studies and require further investigation in human models.
Where it sits
this study against the rest of the igf-1 lr3 (long r3 igf-1) corpusSummary and findings
This study investigated the role of IGF-I in regulating telomerase activity in prostate cancer cell lines LAPC-4, PC-3, and DU-145. IGF-I stimulated telomerase activity by 2- to 10-fold at concentrations of 10 ng/ml to 100 ng/ml. A similar 3-fold enhancement was observed with Long-R3 IGF-I, while hTERT mRNA and protein expression increased 2-fold.
Abstract
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.
Background
Not reported in abstract.
Methods
Not reported in abstract.
Results
Not reported in abstract.
Interpretation
Not reported in abstract.
Limitations
Not reported in abstract.