PMID- 17510413
OWN - NLM
STAT- MEDLINE
DCOM- 20070703
LR  - 20211203
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 10
DP  - 2007 May 15
TI  - Ras transformation of RIE-1 cells activates cap-independent translation of 
      ornithine decarboxylase: regulation by the Raf/MEK/ERK and phosphatidylinositol 
      3-kinase pathways.
PG  - 4834-42
AB  - Ornithine decarboxylase (ODC) is the first and generally rate-limiting enzyme in 
      polyamine biosynthesis. Deregulation of ODC is critical for oncogenic growth, and 
      ODC is a target of Ras. These experiments examine translational regulation of ODC 
      in RIE-1 cells, comparing untransformed cells with those transformed by an 
      activated Ras12V mutant. Analysis of the ODC 5' untranslated region (5'UTR) 
      revealed four splice variants with the presence or absence of two intronic 
      sequences. All four 5'UTR species were found in both cell lines; however, 
      variants containing intronic sequences were more abundant in Ras-transformed 
      cells. All splice variants support internal ribosome entry site (IRES)-mediated 
      translation, and IRES activity is markedly elevated in cells transformed by Ras. 
      Inhibition of Ras effector targets indicated that the ODC IRES element is 
      regulated by the phosphorylation status of the translation factor eIF4E. 
      Dephosphorylation of eIF4E by inhibition of mitogen-activated 
      protein/extracellular signal-regulated kinase (ERK) kinase (MEK) or the eIF4E 
      kinase Mnk1/2 increases ODC IRES activity in both cell lines. When both the 
      Raf/MEK/ERK and phosphatidylinositol 3-kinase/mammalian target of rapamycin 
      pathways are inhibited in normal cells, ODC IRES activity is very low and cells 
      arrest in G(1). When these pathways are inhibited in Ras-transformed cells, cell 
      cycle arrest does not occur and ODC IRES activity increases, helping to maintain 
      high ODC activity.
FAU - Origanti, Sofia
AU  - Origanti S
AD  - Department of Cellular and Molecular Physiology, Penn State College of Medicine, 
      The Milton S. Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
FAU - Shantz, Lisa M
AU  - Shantz LM
LA  - eng
GR  - R01 CA082768/CA/NCI NIH HHS/United States
GR  - CA-82768/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (5' Untranslated Regions)
RN  - 0 (Eukaryotic Initiation Factor-4E)
RN  - 0 (Isoenzymes)
RN  - 0 (MYC protein, human)
RN  - 0 (Proto-Oncogene Proteins c-myc)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (raf Kinases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.25 (MAP Kinase Kinase Kinases)
RN  - EC 4.1.1.17 (Ornithine Decarboxylase)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Animals
MH  - Cell Transformation, Neoplastic/genetics/*metabolism
MH  - Eukaryotic Initiation Factor-4E/metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/*metabolism
MH  - Isoenzymes/biosynthesis/genetics
MH  - MAP Kinase Kinase Kinases/*metabolism
MH  - MAP Kinase Signaling System
MH  - Ornithine Decarboxylase/biosynthesis/genetics/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - Protein Kinases/metabolism
MH  - Proto-Oncogene Proteins c-myc/metabolism
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Rats
MH  - Ribosomes/genetics/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Transfection
MH  - raf Kinases/biosynthesis/genetics/*metabolism
EDAT- 2007/05/19 09:00
MHDA- 2007/07/04 09:00
CRDT- 2007/05/19 09:00
PHST- 2007/05/19 09:00 [pubmed]
PHST- 2007/07/04 09:00 [medline]
PHST- 2007/05/19 09:00 [entrez]
AID - 67/10/4834 [pii]
AID - 10.1158/0008-5472.CAN-06-4627 [doi]
PST - ppublish
SO  - Cancer Res. 2007 May 15;67(10):4834-42. doi: 10.1158/0008-5472.CAN-06-4627.