PMID- 8764119
OWN - NLM
STAT- MEDLINE
DCOM- 19960920
LR  - 20131121
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 56
IP  - 14
DP  - 1996 Jul 15
TI  - Regulation of ornithine decarboxylase in a transformed cell line that 
      overexpresses translation initiation factor eIF-4E.
PG  - 3265-9
AB  - pMV7-4E cells (4E-P2), derived from NIH-3T3 cells, overexpress eIF-4E and exhibit 
      characteristics of transformation, possibly due to translational relief of mRNAs 
      encoding proteins that regulate cell growth. Ornithine decarboxylase (ODC), the 
      rate-limiting enzyme in polyamine biosynthesis, is induced in 4E-P2 cells, and 
      this induction appears to be related to the transformed phenotype of these cells. 
      ODC mRNA contains extensive secondary structure in its 5' untranslated region 
      (5'UTR) and may be regulated by eIF-4E, which melts mRNA secondary structure. To 
      better understand this regulation, cDNA constructs containing the wild-type 5'UTR 
      of ODC or deletion mutants inserted ahead of the luciferase gene were transfected 
      into 4E-P2 and 3T3 cells. Expression of luciferase was higher in 4E-P2 cells in 
      all cases, suggesting that the secondary structure of the ODC 5'UTR inhibits 
      expression in 3T3 cells, and this inhibition is overcome by the high eIF-4E 
      levels in 4E-P2 cells. When a small open reading frame present in the 5'UTR of 
      ODC was destroyed by a point mutation, this luciferase construct was expressed 
      about 6-fold over that containing the wild-type 5'UTR in both cell lines, 
      although both of these 5'UTRs contain the same predicted secondary structure. 
      Thus, factors in addition to eIF-4E may be involved in the regulation of ODC. To 
      examine the differences in ODC regulation by polyamines in normal and transformed 
      cells, the effect of N1,N12-bis(ethyl)spermine (BE-3-4-3) on the synthesis and 
      degradation of ODC was examined. ODC activity in 4E-P2 cells was 10 times less 
      sensitive to reduction by BE-3-4-3 compared to 3T3 cells, suggesting that high 
      ODC levels in eIF-4E-overexpressing cells are the result of decreased regulation 
      by polyamines as well as relief of translational regulation by eIF-4E.
FAU - Shantz, L M
AU  - Shantz LM
AD  - Department of Cellular and Molecular Physiology, Milton S. Hershey Medical 
      Center, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 
      17033, USA.
FAU - Hu, R H
AU  - Hu RH
FAU - Pegg, A E
AU  - Pegg AE
LA  - eng
GR  - CA-18138/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Peptide Initiation Factors)
RN  - 0 (Recombinant Proteins)
RN  - 2FZ7Y3VOQX (Spermine)
RN  - 61345-84-4 (N(1), N(12)-diethylspermine)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Cell Transformation, Neoplastic/metabolism
MH  - Eukaryotic Initiation Factor-4E
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Mice
MH  - Ornithine Decarboxylase/*metabolism
MH  - Peptide Initiation Factors/*metabolism
MH  - Promoter Regions, Genetic
MH  - Recombinant Proteins
MH  - Spermine/*analogs & derivatives/pharmacology
EDAT- 1996/07/15 00:00
MHDA- 1996/07/15 00:01
CRDT- 1996/07/15 00:00
PHST- 1996/07/15 00:00 [pubmed]
PHST- 1996/07/15 00:01 [medline]
PHST- 1996/07/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1996 Jul 15;56(14):3265-9.