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 we have used a synthetic inducible expression system on the basis of the tetracycline repressor of E coli to reversibly express N-myc in a human neuroblastoma cell line in which expression of endogenous N-myc is barely detectable. Like the c-Myc protein, N-Myc up-regulates the expression of both alpha-prothymosin and ornithine decarboxylase. Induction of N-myc increases both the rate of DNA-synthesis and the proliferation rate, and shortens the G1 phase of the cell cycle. A comparison of cell populations in which the presence of N-Myc protein was restricted to different parts of G(zero)/G1 revealed that N-Myc is rate-limiting for cell cycle progression during the first 5 h after serum stimulation of quiescent cells providing direct evidence that Myc-proteins act early after mitogenic stimulation of quiescent cells.
Lutz
W
W
Department of Cytogenetics-0825, German Cancer Research Center, Heidelberg, Germany.
Stöhr
M
M
Schürmann
J
J
Wenzel
A
A
Löhr
A
A
Schwab
M
M
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D001704:Biopolymers; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D016193:G1 Phase; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D009955:Ornithine Decarboxylase / Q000235:genetics*; D011498:Protein Precursors / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D016196:S Phase; D013947:Thymosin / Q000031:analogs & derivatives* / Q000235:genetics; D014157:Transcription Factors; D014407:Tumor Cells, Cultured
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D050976:Basic-Leucine Zipper Transcription Factors; D001704:Biopolymers; D004268:DNA-Binding Proteins; C499330:MAX protein, human; D008934:Mitogens; C067850:Myc associated factor X; D011498:Protein Precursors; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; C040782:prothymosin alpha; D013947:Thymosin; D009955:Ornithine Decarboxylase