Regulation of human ornithine decarboxylase expression following prolonged quiescence: Role for the c‐Myc/Max protein complex

Abstract

WI-38 cells can remain quiescent for long periods of time and still be induced to reenter the cell cycle by the addition of fresh serum. However, the longer these cells remain growth arrested, the more time they require to enter S phase. This prolongation of the prereplicative phase has been localized to a point early in G1, after the induction of "immediate early" G1 genes such as c-fos and c-jun but before maximal expression of "early" G1 genes such as ornithine decarboxylase (ODC). Understanding the molecular basis for ODC mRNA induction can therefore provide information about the molecular events which regulate the progression of cells out of long-term quiescence into G1 and subsequently into DNA synthesis. Studies utilizing electrophoretic mobility shift assays (EMSA) of nuclear extracts from short- and long-term quiescent WI-38 cells identified a region of the human ODC promoter at -491 bp to -474 bp which exhibited a protein binding pattern that correlated with the temporal pattern of ODC mRNA expression. The presence of a CACGTG element within this fragment, studies with antibodies against c-Myc and Max, the use of purified recombinant c-Myc protein in the mobility shift assay, and antisense studies suggest that these proteins can specifically bind this portion of the human ODC promoter in a manner consistent with growth-associated modulation of the expression of ODC and other early G1 genes following prolonged quiescence. These studies suggest a role for the c-Myc/Max protein complex in regulating events involved in the progression of cells out of long-term quiescence into G1 and subsequently into S.

Direct role of nucleotide metabolism in C-MYC-dependent proliferation of melanoma cells

“…Table 1). According to the microarray data, expression of other bona-fide C-MYC targets, such as telomerase reverse transcriptase, 20 cytosolic and mitochondrial serine hydroxymethyltransferases (cSHMT and mSHMT), 16 ornithine decarboxylase 21 and E2F1 22 was affected by 1.5-to 2-fold, while the expression of some other known C-MYC target genes, including cyclin-dependent kinase 4 (CDK4), 15 carbamoylphosphate synthetase 2, aspartate transcarbamylase, dihydroorotase (CAD) 23 and Cyclin D2 24 was not altered.…”

Deregulated expression of a novel component of TFTC/STAGA histone acetyltransferase complexes, rat SGF29, in hepatocellular carcinoma: possible implication for the oncogenic potential of c-Myc

“…In K2 cells, anti-c-Myc Figure 5b). In addition, the effect of rSGF29 on the rat ornithine decarboxylase (ODC) gene promoter activity was analysed using the luciferase reporter gene driven by the -769 to þ 309 rODC promoter region (rODC-Luc) containing 2 E-boxes ( Figure 5c) because the ODC gene is one of the c-Myc target genes (Pena et al, 1993). COS-7 cells were cotransfected with rODCLuc, c-Myc and rSGF29 expression plasmids.…”

Polyamines and cancer: old molecules, new understanding

“…basis for neoplasia in Burkitt's lymphoma 29 . Inappropriate expression of MYC in models of this disease results in inappropriate ODC expression and tumorigenic phenotypes, including increased proliferation and decreased apoptosis 30,31 . In addition, ODC is regulated by the putative oncogene eukaryotic translation initiation factor 4E (eIF4E) in a range of cancers 39 .…”