PMID- 22698407
OWN - NLM
STAT- MEDLINE
DCOM- 20120831
LR  - 20211021
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 21
IP  - 6
DP  - 2012 Jun 12
TI  - Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic 
      neoplasia.
PG  - 836-47
LID - 10.1016/j.ccr.2012.04.024 [doi]
AB  - Stromal responses elicited by early stage neoplastic lesions can promote tumor 
      growth. However, the molecular mechanisms that underlie the early recruitment of 
      stromal cells to sites of neoplasia remain poorly understood. Here, we 
      demonstrate an oncogenic Kras(G12D)-dependent upregulation of GM-CSF in mouse 
      pancreatic ductal epithelial cells (PDECs). An enhanced GM-CSF production is also 
      observed in human PanIN lesions. Kras(G12D)-dependent production of GM-CSF 
      in vivo is required for the recruitment of Gr1(+)CD11b(+) myeloid cells. The 
      suppression of GM-CSF production inhibits the in vivo growth of Kras(G12D)-PDECs, 
      and, consistent with the role of GM-CSF in Gr1(+)CD11b(+) mobilization, this 
      effect is mediated by CD8(+) T cells. These results identify a pathway that links 
      oncogenic activation to the evasion of antitumor immunity.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Pylayeva-Gupta, Yuliya
AU  - Pylayeva-Gupta Y
AD  - Department of Biochemistry and Molecular Pharmacology, New York University School 
      of Medicine, New York, NY 10016, USA.
FAU - Lee, Kyoung Eun
AU  - Lee KE
FAU - Hajdu, Cristina H
AU  - Hajdu CH
FAU - Miller, George
AU  - Miller G
FAU - Bar-Sagi, Dafna
AU  - Bar-Sagi D
LA  - eng
GR  - P30 CA016087/CA/NCI NIH HHS/United States
GR  - R56 CA055360/CA/NCI NIH HHS/United States
GR  - CA055360/CA/NCI NIH HHS/United States
GR  - R01 CA055360/CA/NCI NIH HHS/United States
GR  - 5 P30CA016087-31/CA/NCI NIH HHS/United States
GR  - R37 CA055360/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 (CD11b Antigen)
RN  - 0 (Gr-1 protein, mouse)
RN  - 0 (Receptors, Chemokine)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor)
RN  - EC 3.6.5.2 (Hras protein, mouse)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
CIN - Nat Rev Gastroenterol Hepatol. 2012 Aug;9(8):426. PMID: 22733349
CIN - Nat Rev Cancer. 2012 Aug;12(8):510-1. PMID: 22810812
CIN - Nat Rev Immunol. 2012 Aug;12(8):555. PMID: 22814510
MH  - Adenocarcinoma/genetics/metabolism/pathology
MH  - Animals
MH  - CD11b Antigen/metabolism
MH  - CD8-Positive T-Lymphocytes/metabolism
MH  - Carcinoma, Pancreatic Ductal/genetics/metabolism/pathology
MH  - *Cell Transformation, Neoplastic
MH  - Cells, Cultured
MH  - Epithelial Cells/*metabolism
MH  - Granulocyte-Macrophage Colony-Stimulating Factor/genetics/*metabolism
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Immunoblotting
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microscopy, Fluorescence
MH  - Myeloid Cells/metabolism
MH  - Pancreatic Ducts/cytology/*metabolism
MH  - Pancreatic Neoplasms/genetics/*metabolism/pathology
MH  - Proto-Oncogene Proteins p21(ras)/genetics/*metabolism
MH  - RNA Interference
MH  - Receptors, Chemokine/metabolism
PMC - PMC3721510
MID - NIHMS373326
COIS- COMPETING FINANCIAL INTERESTS The authors declare no competing financial 
      interests.
EDAT- 2012/06/16 06:00
MHDA- 2012/09/01 06:00
PMCR- 2013/07/24
CRDT- 2012/06/16 06:00
PHST- 2011/07/13 00:00 [received]
PHST- 2012/02/05 00:00 [revised]
PHST- 2012/04/09 00:00 [accepted]
PHST- 2012/06/16 06:00 [entrez]
PHST- 2012/06/16 06:00 [pubmed]
PHST- 2012/09/01 06:00 [medline]
PHST- 2013/07/24 00:00 [pmc-release]
AID - S1535-6108(12)00166-3 [pii]
AID - 10.1016/j.ccr.2012.04.024 [doi]
PST - ppublish
SO  - Cancer Cell. 2012 Jun 12;21(6):836-47. doi: 10.1016/j.ccr.2012.04.024.