PMID- 17468756
OWN - NLM
STAT- MEDLINE
DCOM- 20070814
LR  - 20220321
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 39
IP  - 6
DP  - 2007 Jun
TI  - MMTV insertional mutagenesis identifies genes, gene families and pathways 
      involved in mammary cancer.
PG  - 759-69
AB  - We performed a high-throughput retroviral insertional mutagenesis screen in mouse 
      mammary tumor virus (MMTV)-induced mammary tumors and identified 33 common 
      insertion sites, of which 17 genes were previously not known to be associated 
      with mammary cancer and 13 had not previously been linked to cancer in general. 
      Although members of the Wnt and fibroblast growth factors (Fgf) families were 
      frequently tagged, our exhaustive screening for MMTV insertion sites uncovered a 
      new repertoire of candidate breast cancer oncogenes. We validated one of these 
      genes, Rspo3, as an oncogene by overexpression in a p53-deficient mammary 
      epithelial cell line. The human orthologs of the candidate oncogenes were 
      frequently deregulated in human breast cancers and associated with several tumor 
      parameters. Computational analysis of all MMTV-tagged genes uncovered specific 
      gene families not previously associated with cancer and showed a significant 
      overrepresentation of protein domains and signaling pathways mainly associated 
      with development and growth factor signaling. Comparison of all tagged genes in 
      MMTV and Moloney murine leukemia virus-induced malignancies showed that both 
      viruses target mostly different genes that act predominantly in distinct 
      pathways.
FAU - Theodorou, Vassiliki
AU  - Theodorou V
AD  - Division of Molecular Genetics, The Netherlands Cancer Institute, Plesmanlaan 
      121, 1066 CX Amsterdam, The Netherlands.
FAU - Kimm, Melanie A
AU  - Kimm MA
FAU - Boer, Mandy
AU  - Boer M
FAU - Wessels, Lodewyk
AU  - Wessels L
FAU - Theelen, Wendy
AU  - Theelen W
FAU - Jonkers, Jos
AU  - Jonkers J
FAU - Hilkens, John
AU  - Hilkens J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070429
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Animals
MH  - Cell Transformation, Neoplastic
MH  - Epithelium/metabolism
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Regulation, Neoplastic
MH  - Genes, Neoplasm/*genetics
MH  - Mammary Neoplasms, Experimental/*genetics/*metabolism/pathology
MH  - Mammary Tumor Virus, Mouse/*genetics
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Multigene Family/*genetics
MH  - Mutagenesis, Insertional/*genetics
MH  - Oncogenic Viruses/genetics
MH  - RNA, Messenger/metabolism
MH  - *Signal Transduction
MH  - Tumor Suppressor Protein p53/genetics/metabolism
MH  - Virus Integration
EDAT- 2007/05/01 09:00
MHDA- 2007/08/19 09:00
CRDT- 2007/05/01 09:00
PHST- 2006/07/07 00:00 [received]
PHST- 2007/03/29 00:00 [accepted]
PHST- 2007/05/01 09:00 [pubmed]
PHST- 2007/08/19 09:00 [medline]
PHST- 2007/05/01 09:00 [entrez]
AID - ng2034 [pii]
AID - 10.1038/ng2034 [doi]
PST - ppublish
SO  - Nat Genet. 2007 Jun;39(6):759-69. doi: 10.1038/ng2034. Epub 2007 Apr 29.