PMID- 19816943
OWN - NLM
STAT- MEDLINE
DCOM- 20100225
LR  - 20211020
IS  - 1097-0215 (Electronic)
IS  - 0020-7136 (Print)
IS  - 0020-7136 (Linking)
VI  - 126
IP  - 6
DP  - 2010 Mar 15
TI  - The Arf-inducing transcription factor Dmp1 encodes a transcriptional activator of 
      amphiregulin, thrombospondin-1, JunB and Egr1.
PG  - 1403-16
LID - 10.1002/ijc.24938 [doi]
AB  - Dmp1 (Dmtf1) encodes a Myb-like transcription factor implicated in tumor 
      suppression through direct activation of the Arf-p53 pathway. The human DMP1 gene 
      is frequently deleted in non-small cell lung cancers, especially those that 
      retain wild-type INK4a/ARF and/or p53. To identify novel genes that are regulated 
      by Dmp1, transcriptional profiles of lung tissue from Dmp1-null and wild-type 
      mice were generated using the GeneChip Microarray. Comparative analysis of gene 
      expression changes between the two groups resulted in identification of numerous 
      genes that may be regulated by Dmp1. Notably, amphiregulin (Areg), 
      thrombospondin-1 (Tsp-1), JunB, Egr1, adrenomedullin (Adm), Bcl-3 and methyl-CpG 
      binding domain protein 1 (Mbd1) were downregulated in the lungs from Dmp1-null 
      mice while Gas1 and Ect2 genes were upregulated. These target genes were chosen 
      for further analyses since they are involved in cell proliferation, 
      transcription, angiogenesis/metastasis, apoptosis, or DNA methylation, and thus 
      could account for the tumor suppressor phenotype of Dmp1. Dmp1 directly bound to 
      the genomic loci of Areg, Tsp-1, JunB and Egr1. Significant upregulation or 
      downregulation of the novel Dmp1 target genes was observed upon transient 
      expression of Dmp1 in alveolar epithelial cells, an effect which was nullified by 
      the inhibition of de novo mRNA synthesis. Interestingly, these genes and their 
      protein products were significantly downregulated or upregulated in the lungs 
      from Dmp1-heterozygous mice as well. Identification of novel Dmp1 target genes 
      not only provides insights into the effects of Dmp1 on global gene expression, 
      but also sheds light on the mechanism of haploid insufficiency of Dmp1 in tumor 
      suppression.
FAU - Mallakin, Ali
AU  - Mallakin A
AD  - Department of Pathology, Wake Forest University Health Sciences, Medical Center 
      Boulevard, Winston-Salem, NC 27157, USA.
FAU - Sugiyama, Takayuki
AU  - Sugiyama T
FAU - Kai, Fumitake
AU  - Kai F
FAU - Taneja, Pankaj
AU  - Taneja P
FAU - Kendig, Robert D
AU  - Kendig RD
FAU - Frazier, Donna P
AU  - Frazier DP
FAU - Maglic, Dejan
AU  - Maglic D
FAU - Matise, Lauren A
AU  - Matise LA
FAU - Willingham, Mark C
AU  - Willingham MC
FAU - Inoue, Kazushi
AU  - Inoue K
LA  - eng
GR  - R01 CA106314-06A1/CA/NCI NIH HHS/United States
GR  - P30 CA012197/CA/NCI NIH HHS/United States
GR  - R01 CA106314/CA/NCI NIH HHS/United States
GR  - 5R01CA106314/CA/NCI NIH HHS/United States
GR  - P30CA12197/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Cancer
JT  - International journal of cancer
JID - 0042124
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Areg protein, mouse)
RN  - 0 (Cdkn2a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Dmtf1 protein, mouse)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Early Growth Response Protein 1)
RN  - 0 (Egr1 protein, mouse)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Thrombospondin 1)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Amphiregulin
MH  - Animals
MH  - Blotting, Western
MH  - Chromatin Immunoprecipitation
MH  - Cluster Analysis
MH  - Cyclin-Dependent Kinase Inhibitor p16/*genetics
MH  - EGF Family of Proteins
MH  - Early Growth Response Protein 1/*genetics/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - Female
MH  - Gene Expression Profiling
MH  - Glycoproteins/*genetics/metabolism
MH  - Immunohistochemistry
MH  - Intercellular Signaling Peptides and Proteins/*genetics/metabolism
MH  - Lung/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oligonucleotide Array Sequence Analysis
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-jun/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Thrombospondin 1/*genetics/metabolism
MH  - Trans-Activators/genetics/metabolism
MH  - Transcription Factors/*genetics/metabolism
PMC - PMC2836939
MID - NIHMS163811
EDAT- 2009/10/10 06:00
MHDA- 2010/02/26 06:00
PMCR- 2011/03/15
CRDT- 2009/10/10 06:00
PHST- 2009/10/10 06:00 [entrez]
PHST- 2009/10/10 06:00 [pubmed]
PHST- 2010/02/26 06:00 [medline]
PHST- 2011/03/15 00:00 [pmc-release]
AID - 10.1002/ijc.24938 [doi]
PST - ppublish
SO  - Int J Cancer. 2010 Mar 15;126(6):1403-16. doi: 10.1002/ijc.24938.