PMID- 17210685
OWN - NLM
STAT- MEDLINE
DCOM- 20070130
LR  - 20191210
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 67
IP  - 1
DP  - 2007 Jan 1
TI  - Transcriptional cooperation between the transforming growth factor-beta and Wnt 
      pathways in mammary and intestinal tumorigenesis.
PG  - 75-84
AB  - Transforming growth factor-beta (TGF-beta) and Wnt ligands function in numerous 
      developmental processes, and alterations of both signaling pathways are 
      associated with common pathologic conditions, including cancer. To obtain insight 
      into the extent of interdependence of the two signaling cascades in regulating 
      biological responses, we used an oligonucleotide microarray approach to identify 
      Wnt and TGF-beta target genes using normal murine mammary gland epithelial cells 
      as a model. Combination treatment of TGF-beta and Wnt revealed a novel 
      transcriptional program that could not have been predicted from single ligand 
      treatments and included a cohort of genes that were cooperatively induced by both 
      pathways. These included both novel and known components or modulators of 
      TGF-beta and Wnt pathways, suggesting that mutual feedback is a feature of the 
      coordinated activities of the ligands. The majority of the cooperative targets 
      display increased expression in tumors derived from either Min (many intestinal 
      neoplasia) or mouse mammary tumor virus (MMTV)-Wnt1 mice, two models of 
      Wnt-induced tumors, with nine of these genes (Ankrd1, Ccnd1, Ctgf, Gpc1, Hs6st2, 
      IL11, Inhba, Mmp14, and Robo1) showing increases in both. Reduction of TGF-beta 
      signaling by expression of a dominant-negative TGF-beta type II receptor in 
      bigenic MMTV-Wnt1/DNIIR mice increased mammary tumor latency and was correlated 
      with a decrease in expression of Gpc1, Inhba, and Robo1, three of the 
      TGF-beta/Wnt cooperative targets. Our results indicate that the TGF-beta and 
      Wnt/beta-catenin pathways are firmly intertwined and generate a unique gene 
      expression pattern that can contribute to tumor progression.
FAU - Labbe, Etienne
AU  - Labbe E
AD  - Departments of Medical Biophysics and Biochemistry, University of Toronto, 160 
      College Street, Toronto, Ontario, Canada.
FAU - Lock, Lisa
AU  - Lock L
FAU - Letamendia, Ainhoa
AU  - Letamendia A
FAU - Gorska, Agnieszka E
AU  - Gorska AE
FAU - Gryfe, Robert
AU  - Gryfe R
FAU - Gallinger, Steven
AU  - Gallinger S
FAU - Moses, Harold L
AU  - Moses HL
FAU - Attisano, Liliana
AU  - Attisano L
LA  - eng
GR  - CA 085492/CA/NCI NIH HHS/United States
GR  - CA 102162/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  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Wnt Proteins)
RN  - 0 (Wnt3 Protein)
SB  - IM
MH  - Adenoma/genetics/metabolism/pathology
MH  - Animals
MH  - Cell Transformation, Neoplastic/*genetics/metabolism/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Intestinal Neoplasms/*genetics/metabolism/pathology
MH  - L Cells
MH  - Mammary Neoplasms, Experimental/*genetics/metabolism/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Signal Transduction
MH  - Transcription, Genetic
MH  - Transforming Growth Factor beta/*genetics/metabolism
MH  - Wnt Proteins/*genetics/metabolism
MH  - Wnt3 Protein
EDAT- 2007/01/11 09:00
MHDA- 2007/01/31 09:00
CRDT- 2007/01/11 09:00
PHST- 2007/01/11 09:00 [pubmed]
PHST- 2007/01/31 09:00 [medline]
PHST- 2007/01/11 09:00 [entrez]
AID - 67/1/75 [pii]
AID - 10.1158/0008-5472.CAN-06-2559 [doi]
PST - ppublish
SO  - Cancer Res. 2007 Jan 1;67(1):75-84. doi: 10.1158/0008-5472.CAN-06-2559.