PMID- 25269081
OWN - NLM
STAT- MEDLINE
DCOM- 20151221
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - NR4A1 promotes PDGF-BB-induced cell colony formation in soft agar.
PG  - e109047
LID - 10.1371/journal.pone.0109047 [doi]
LID - e109047
AB  - The fibroblast mitogen platelet-derived growth factor -BB (PDGF-BB) induces a 
      transient expression of the orphan nuclear receptor NR4A1 (also named Nur77, TR3 
      or NGFIB). The aim of the present study was to investigate the pathways through 
      which NR4A1 is induced by PDGF-BB and its functional role. We demonstrate that in 
      PDGF-BB stimulated NIH3T3 cells, the MEK1/2 inhibitor CI-1040 strongly represses 
      NR4A1 expression, whereas Erk5 downregulation delays the expression, but does not 
      block it. Moreover, we report that treatment with the NF-kappaB inhibitor BAY11-7082 
      suppresses NR4A1 mRNA and protein expression. The majority of NR4A1 in NIH3T3 was 
      found to be localized in the cytoplasm and only a fraction was translocated to 
      the nucleus after continued PDGF-BB treatment. Silencing NR4A1 slightly increased 
      the proliferation rate of NIH3T3 cells; however, it did not affect the 
      chemotactic or survival abilities conferred by PDGF-BB. Moreover, overexpression 
      of NR4A1 promoted anchorage-independent growth of NIH3T3 cells and the 
      glioblastoma cell lines U-105MG and U-251MG. Thus, whereas NR4A1, induced by 
      PDGF-BB, suppresses cell growth on a solid surface, it increases 
      anchorage-independent growth.
FAU - Eger, Glenda
AU  - Eger G
AD  - Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden.
FAU - Papadopoulos, Natalia
AU  - Papadopoulos N
AD  - Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden.
FAU - Lennartsson, Johan
AU  - Lennartsson J
AD  - Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden.
FAU - Heldin, Carl-Henrik
AU  - Heldin CH
AD  - Ludwig Institute for Cancer Research, Uppsala University, Uppsala, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140930
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide)
RN  - 0 (3-(4-methylphenylsulfonyl)-2-propenenitrile)
RN  - 0 (Benzamides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nitriles)
RN  - 0 (Nr4a1 protein, mouse)
RN  - 0 (Nuclear Receptor Subfamily 4, Group A, Member 1)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Sulfones)
RN  - 1B56C968OA (Becaplermin)
RN  - 9002-18-0 (Agar)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 7)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Map2k2 protein, mouse)
SB  - IM
MH  - Agar
MH  - Animals
MH  - Becaplermin
MH  - Benzamides/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Chemotaxis/drug effects
MH  - Gene Expression Regulation
MH  - Humans
MH  - MAP Kinase Kinase 1/antagonists & inhibitors/genetics/metabolism
MH  - MAP Kinase Kinase 2/antagonists & inhibitors/genetics/metabolism
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 7/antagonists & inhibitors/genetics/metabolism
MH  - NF-kappa B/antagonists & inhibitors/genetics/metabolism
MH  - NIH 3T3 Cells
MH  - Neuroglia/drug effects/*metabolism/pathology
MH  - Nitriles/pharmacology
MH  - Nuclear Receptor Subfamily 4, Group A, Member 1/antagonists & 
      inhibitors/*genetics/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Proto-Oncogene Proteins c-sis/*pharmacology
MH  - RNA, Messenger/antagonists & inhibitors/*genetics/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Signal Transduction
MH  - Sulfones/pharmacology
PMC - PMC4182636
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/10/01 06:00
MHDA- 2015/12/22 06:00
PMCR- 2014/09/30
CRDT- 2014/10/01 06:00
PHST- 2014/05/19 00:00 [received]
PHST- 2014/08/30 00:00 [accepted]
PHST- 2014/10/01 06:00 [entrez]
PHST- 2014/10/01 06:00 [pubmed]
PHST- 2015/12/22 06:00 [medline]
PHST- 2014/09/30 00:00 [pmc-release]
AID - PONE-D-14-21276 [pii]
AID - 10.1371/journal.pone.0109047 [doi]
PST - epublish
SO  - PLoS One. 2014 Sep 30;9(9):e109047. doi: 10.1371/journal.pone.0109047. 
      eCollection 2014.