Deregulated c-myc expression in quiescent CHO cells induces target gene transcription and subsequent apoptotic phenotype.

Human c-myc cDNA was fused with the hormone-binding domain (HBD) cDNA of murine estrogen receptor gene and the chimeric gene was introduced into the CHO cells. The fusion protein, c-MycER, becomes activated when the synthetic steroid, 4-hydroxy-tamoxifen (OHT), binds HBD. Activated c-MycER, likely c-Myc, can induce quiescent CHO cells reentry into S phase and subsequent cell death under serum-free condition. In addition, the expression of some proposed c-myc target genes such as ODC, MrDb, cad, rcc1 and rcl were found to increase upon OHT induction before S phase entry and apoptosis, indicating that these target genes are involved in cell cycle regulation and/or apoptosis control. However, the mutant D106-143c-MycER protein does not have above activities.