PMID- 19732721
OWN - NLM
STAT- MEDLINE
DCOM- 20091014
LR  - 20240417
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 16
IP  - 3
DP  - 2009 Sep 8
TI  - Colitis-associated colorectal cancer driven by T-bet deficiency in dendritic 
      cells.
PG  - 208-19
LID - 10.1016/j.ccr.2009.07.015 [doi]
AB  - We previously described a mouse model of ulcerative colitis linked to T-bet 
      deficiency in the innate immune system. Here, we report that the majority of 
      T-bet(-/-)RAG2(-/-) ulcerative colitis (TRUC) mice spontaneously progress to 
      colonic dysplasia and rectal adenocarcinoma solely as a consequence of 
      MyD88-independent intestinal inflammation. Dendritic cells (DCs) are necessary 
      cellular effectors for a proinflammatory program that is carcinogenic. Whereas 
      these malignancies arise in the setting of a complex inflammatory environment, 
      restoration of T-bet selectively in DCs was sufficient to reduce colonic 
      inflammation and prevent the development of neoplasia. TRUC colitis-associated 
      colorectal cancer resembles the human disease and provides ample opportunity to 
      probe how inflammation drives colorectal cancer development and to test 
      preventative and therapeutic strategies preclinically.
FAU - Garrett, Wendy S
AU  - Garrett WS
AD  - Department of Immunology and Infectious Diseases, Harvard School of Public 
      Health, Boston, MA 02115, USA. wendy_garrett@dfci.harvard.edu
FAU - Punit, Shivesh
AU  - Punit S
FAU - Gallini, Carey A
AU  - Gallini CA
FAU - Michaud, Monia
AU  - Michaud M
FAU - Zhang, Dorothy
AU  - Zhang D
FAU - Sigrist, Kirsten S
AU  - Sigrist KS
FAU - Lord, Graham M
AU  - Lord GM
FAU - Glickman, Jonathan N
AU  - Glickman JN
FAU - Glimcher, Laurie H
AU  - Glimcher LH
LA  - eng
GR  - R01 CA112663-10/CA/NCI NIH HHS/United States
GR  - R01 CA112663/CA/NCI NIH HHS/United States
GR  - K08 AI078942/AI/NIAID NIH HHS/United States
GR  - CA112663/CA/NCI NIH HHS/United States
GR  - P50 CA127003/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 Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Rag2 protein, mouse)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (T-box transcription factor TBX21)
SB  - IM
MH  - Animals
MH  - Colitis, Ulcerative/*immunology/pathology
MH  - Colon/immunology/pathology
MH  - Colorectal Neoplasms/*immunology
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Dendritic Cells/*immunology/pathology
MH  - Disease Models, Animal
MH  - Humans
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Knockout
MH  - T-Box Domain Proteins/*immunology
PMC - PMC2740755
MID - NIHMS136360
EDAT- 2009/09/08 06:00
MHDA- 2009/10/15 06:00
PMCR- 2010/09/08
CRDT- 2009/09/08 06:00
PHST- 2009/03/11 00:00 [received]
PHST- 2009/05/29 00:00 [revised]
PHST- 2009/07/22 00:00 [accepted]
PHST- 2009/09/08 06:00 [entrez]
PHST- 2009/09/08 06:00 [pubmed]
PHST- 2009/10/15 06:00 [medline]
PHST- 2010/09/08 00:00 [pmc-release]
AID - S1535-6108(09)00250-5 [pii]
AID - 10.1016/j.ccr.2009.07.015 [doi]
PST - ppublish
SO  - Cancer Cell. 2009 Sep 8;16(3):208-19. doi: 10.1016/j.ccr.2009.07.015.