Mechanism of T-oligo-induced cell cycle arrest in Mia-Paca pancreatic cancer cells

✍ Scribed by Andrew M. Rankin; Sibaji Sarkar; Douglas V. Faller

• Publisher: John Wiley and Sons
• Year: 2012
• Tongue: English
• Weight: 782 KB
• Volume: 227
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.22997

✦ Synopsis

Abstract

DNA oligonucleotides with sequence homology to human telomeric DNA (T‐oligo) induce cell cycle arrest, followed by apoptosis, senescence, or autophagy in a human cancer cell type‐specific manner. T‐oligo has potential as a new therapeutic strategy in oncology because of its ability to target certain types of tumor cells while sparing normal ones. In the present study, we demonstrate the T‐oligo‐induced S‐phase cell cycle arrest in four pancreatic cancer cell lines. To further contribute to the mechanistic understanding of T‐oligo, we also identify cyclin dependent kinase 2 (cdk2) as a functional mediator in the T‐oligo‐induced cell cycle arrest of pancreatic cancer cells. Ectopic expression of a constitutively active cdk2 mutant abrogates T‐oligo‐induced cell cycle arrest in these tumor cells while knockdown of cdk2 expression alone recapitulates the T‐oligo effect. Finally, we demonstrate the dispensability of T‐oligo‐induced ATM/ATR‐mediated DNA damage response‐signaling pathways, which have long been considered functional in the T‐oligo signaling mechanism. J. Cell. Physiol. 227: 2586–2594, 2012. © 2011 Wiley Periodicals, Inc.