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KMID : 0613820030130050642
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Journal of Life Science
2003 Volume.13 No. 5 p.642 ~ p.650
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Inhibition of pRB Phosphorylation and Induction of p21WAF1/CIP1 Occur During cAMP-induced Growth Arrest in Human Neuroblastoma Cells
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Choi Yung-Hyun
Lee Sang-Hyun
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Abstract
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To develop a new approach to the treatment of neuroblastoma cells we evaluated the effect of cAMP on the Ewing’s sarcoma cell line CHP-100. We observed that the proliferation-inhibitory effect of cAMP analogs was due to cell cycle arrest and induction of apoptosis, which was confirmed by observing the morphological changes and DNA fragmentation. DNA flow cytometric analysis revealed that cAMP arrested the cell cycle progression at the G1 phase, which effects were associated with inhibition of phosphorylation of retinoblastoma protein (pRB) and enhanced binding of pRB and the transcription factor E2F-1. cAMP also suppressed the cyclin-dependent kinase (Cdk) 2 and cyclin E- associated kinase activity without changes of their expressions. Furthermore, cAMP induced the levels of Cdk inhibitor p21WAF1/CIP1 expression and p21 proteins induced by cAMP were associated with Cdk2. Overall, our results identify a combined mechanism involving the inhibition of pRB phosphorylation and induction of p21 as targets for cAMP, and this may explain some of its anti-cancer effects.
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KEYWORD
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cAMP, Apoptosis, G1 arrest, pRB, p21
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