Cdc42/Rac1 participates in the control of telomerase activity in human nasopharyngeal cancer cells

Telomerase, a specialized ribonucleoprotein reverse transcriptase that directs the synthesis of telomeric DNA, is repressed in normal human somatic cells, but is activated in most cancers. Little is known concerning how telomerase activity is activated and maintained in cancer cells. We have previously shown that protein kinase C-zeta (PKCzeta) controls telomerase activity in nasopharyngeal cancer (NPC) cells. Since PKCzeta activity is known to be modulated by Cdc42/Rac1, we investigated the effects of inhibiting Cdc42 and Rac1 on the telomerase activity of NPC-076 cells. Treatment of NPC cells with antisense oligonucleotides against Cdc42 or Rac1 produced an inhibition of telomerase activity. Similarly, transient expression of dominant-negative mutants of Cdc42 or Rac1, but not the wild-type Cdc42 or Rac1, also produced an inhibition of telomerase activity in NPC cells. This inhibition of telomerase activity is not associated with a transcriptional down-regulation of hTERT, the key regulator of telomerase. We suggest that Cdc42/Rac1 participates in the posttranscriptional control of telomerase activity in NPC cells. (C) 2004 Elsevier Ireland Ltd. All rights reserved.