کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2515599 | 1118535 | 2007 | 12 صفحه PDF | دانلود رایگان |
Targeting of human telomerase reverse transcriptase (hTERT) by different small interfering RNAs (siRNAs) resulted in a variable degree of telomerase activity inhibition in PC-3 and DU145 prostate cancer cells. In addition, transfection with siRNA5 and siRNA41, which caused high levels (∼80 and ∼55%, respectively) of enzyme activity inhibition in both cell lines, led to a marked reduction of hTERT mRNA and protein expression and a significant inhibition of cell proliferation within a few days, without concomitant telomere shortening or telomeric 3′ overhang impairment. Such an antiproliferative effect was not ascribable to the activation of non-specific responses, since siRNA5 and siRNA41 did not induce the expression of 2′–5′ oligoadenylate synthetase-1 and were able to cause a significant growth impairment also in HCT 116 colon cancer cells, which have a defective interferon pathway. Cell growth inhibition was indeed associated with hTERT down-regulation, as it was almost completely rescued in siRNA-treated HCT 116 cells co-transfected with an hTERT-expressing vector. Moreover, siRNA5 and siRNA41 failed to affect the proliferation of hTERT-negative U2-OS osteosarcoma cells. Interestingly, transfection with siRNA5 significantly reduced the tumorigenic and growth potential of PC-3 cells when xenotransplanted into nude mice. Such data suggest siRNA-mediated hTERT down-regulation as an efficient strategy to impair prostate cancer cell growth.
Journal: Biochemical Pharmacology - Volume 73, Issue 11, 1 June 2007, Pages 1703–1714