PMID- 17951404
OWN - NLM
STAT- MEDLINE
DCOM- 20071217
LR  - 20150813
IS  - 1541-7786 (Print)
IS  - 1541-7786 (Linking)
VI  - 5
IP  - 10
DP  - 2007 Oct
TI  - Mouse embryo fibroblasts lacking the tumor suppressor menin show altered 
      expression of extracellular matrix protein genes.
PG  - 1041-51
AB  - Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant familial 
      cancer syndrome characterized primarily by endocrine tumors of the parathyroids, 
      anterior pituitary, and enteropancreatic endocrine tissues. Affected individuals 
      carry a germ-line loss-of-function mutation of the MEN1 gene, and tumors arise 
      after loss of the second allele. Homozygous loss of Men1 in the germ line of mice 
      results in early embryonic lethality, with defective development of neural tube, 
      heart, liver, and craniofacial structures. We generated immortalized wild-type 
      (WT) and menin-null mouse embryo fibroblast (MEF) cell lines and evaluated their 
      characteristics, including global expression patterns. The WT and menin-null cell 
      lines were aneuploid, and the nulls did not display tumorigenic characteristics 
      in soft agar assay. Expression arrays in menin-null MEFs revealed altered 
      expression of several extracellular matrix proteins that are critical in 
      organogenesis. Specifically, transcripts for fibulin 2 (Fbln2), periostin 
      (Postn), and versican [chondroitin sulfate proteoglycan (Cspg2)], genes critical 
      for the developing heart and known to be induced by transforming growth 
      factor-beta (TGF-beta), were decreased in their expression in menin-null MEFs. 
      Fbln2 expression was the most affected, and the reduction in menin-null MEFs for 
      Fbln2, Postn, and Cspg2 was 16.18-, 5.37-, and 2.15-fold, respectively. 
      Menin-null MEFs also showed poor response to TGF-beta-induced Smad3-mediated 
      transcription in a reporter assay, supporting a role for menin in this pathway. 
      Postn and Cspg2 expression in WT, unlike in null MEFs, increased on TGF-beta 
      treatment. The expression changes associated with the loss of the tumor 
      suppressor menin provide insights into the defective organogenesis observed 
      during early embryonic development in Men1-null mouse embryos.
FAU - Ji, Youngmi
AU  - Ji Y
AD  - Genome Technology Branch, National Human Genome Research Institute, NIH, 
      Bethesda, Maryland 20892, USA.
FAU - Prasad, Nijaguna B
AU  - Prasad NB
FAU - Novotny, Elizabeth A
AU  - Novotny EA
FAU - Kaur, Sukhbir
AU  - Kaur S
FAU - Elkahloun, Abdel
AU  - Elkahloun A
FAU - Chen, Yidong
AU  - Chen Y
FAU - Zhang, Rui-Zhu
AU  - Zhang RZ
FAU - Chu, Mon-Li
AU  - Chu ML
FAU - Agarwal, Sunita K
AU  - Agarwal SK
FAU - Marx, Stephen J
AU  - Marx SJ
FAU - Collins, Francis S
AU  - Collins FS
FAU - Chandrasekharappa, Settara C
AU  - Chandrasekharappa SC
LA  - eng
GR  - GM55625/GM/NIGMS NIH HHS/United States
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Animals
MH  - Embryo, Mammalian/cytology/drug effects/*metabolism
MH  - Extracellular Matrix Proteins/*genetics
MH  - Fibroblasts/drug effects/metabolism
MH  - *Gene Expression Regulation, Developmental
MH  - Mice
MH  - Organogenesis/genetics
MH  - Proto-Oncogene Proteins/genetics/*physiology
MH  - Transforming Growth Factor beta/pharmacology
MH  - Tumor Suppressor Proteins/genetics/*physiology
EDAT- 2007/10/24 09:00
MHDA- 2007/12/18 09:00
CRDT- 2007/10/24 09:00
PHST- 2007/10/24 09:00 [pubmed]
PHST- 2007/12/18 09:00 [medline]
PHST- 2007/10/24 09:00 [entrez]
AID - 5/10/1041 [pii]
AID - 10.1158/1541-7786.MCR-06-0379 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2007 Oct;5(10):1041-51. doi: 10.1158/1541-7786.MCR-06-0379.