CONDITIONAL EXPRESSION OF N-MYC IN HUMAN NEUROBLASTOMA-CELLS INCREASES EXPRESSION OF ALPHA-PROTHYMOSIN AND ORNITHINE DECARBOXYLASE AND ACCELERATES PROGRESSION INTO S-PHASE EARLY AFTER MITOGENIC STIMULATION OF QUIESCENT CELLS

To elucidate the contribution of the N-Myc protein to neuroblastomas w e have used a synthetic inducible expression system on the basis of th e tetracycline repressor of E coli to reversibly express N-myc in a hu man neuroblastoma cell line in which expression of endogenous N-myc is barely detectable. Like the c-Myc protein, N-Myc up-regulates the exp ression of both alpha-prothymosin and ornithine decarboxylase. Inducti on of N-myc increases both the rate of DNA-synthesis and the prolifera tion rate, and shortens the G(1) phase of the cell cycle. A comparison of cell populations in which the presence of N-Myc protein was restri cted to different parts of G(0)/G(1) revealed that N-Myc is rate-limit ing for cell cycle progression during the first 5 h after serum stimul ation of quiescent cells providing direct evidence that Myc-proteins a ct early after mitogenic stimulation of quiescent cells.