PMID- 21159656
OWN - NLM
STAT- MEDLINE
DCOM- 20110120
LR  - 20211103
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 70
IP  - 24
DP  - 2010 Dec 15
TI  - The canonical NF-kappaB pathway governs mammary tumorigenesis in transgenic mice 
      and tumor stem cell expansion.
PG  - 10464-73
LID - 10.1158/0008-5472.CAN-10-0732 [doi]
AB  - The role of mammary epithelial cell (MEC) NF-kappaB in tumor progression in vivo is 
      unknown, as murine NF-kappaB components and kinases either are required for murine 
      survival or interfere with normal mammary gland development. As NF-kappaB inhibitors 
      block both tumor-associated macrophages (TAM) and MEC NF-kappaB, the importance of 
      MEC NF-kappaB to tumor progression in vivo remained to be determined. Herein, an 
      MEC-targeted inducible transgenic inhibitor of NF-kappaB (IkappaBalphaSR) was developed in 
      ErbB2 mammary oncomice. Inducible suppression of NF-kappaB in the adult mammary 
      epithelium delayed the onset and number of new tumors. Within similar sized 
      breast tumors, TAM and tumor neoangiogenesis was reduced. Coculture experiments 
      demonstrated MEC NF-kappaB enhanced TAM recruitment. Genome-wide expression and 
      proteomic analysis showed that IkappaBalphaSR inhibited tumor stem cell pathways. IkappaBalphaSR 
      inhibited breast tumor stem cell markers in transgenic tumors, reduced stem cell 
      expansion in vitro, and repressed expression of Nanog and Sox2 in vivo and in 
      vitro. MEC NF-kappaB contributes to mammary tumorigenesis. As we show that NF-kappaB 
      contributes to expansion of breast tumor stem cells and heterotypic signals that 
      enhance TAM and vasculogenesis, these processes may contribute to NF-kappaB-dependent 
      mammary tumorigenesis.
CI  - (c)2010 AACR.
FAU - Liu, Manran
AU  - Liu M
AD  - Department of Cancer Biology, Kimmel Cancer Center, Thomas Jefferson University, 
      Philadelphia, PA 19107, USA.
FAU - Sakamaki, Toshiyuki
AU  - Sakamaki T
FAU - Casimiro, Mathew C
AU  - Casimiro MC
FAU - Willmarth, Nicole E
AU  - Willmarth NE
FAU - Quong, Andrew A
AU  - Quong AA
FAU - Ju, Xiaoming
AU  - Ju X
FAU - Ojeifo, John
AU  - Ojeifo J
FAU - Jiao, Xuanmao
AU  - Jiao X
FAU - Yeow, Wen-Shuz
AU  - Yeow WS
FAU - Katiyar, Sanjay
AU  - Katiyar S
FAU - Shirley, L Andrew
AU  - Shirley LA
FAU - Joyce, David
AU  - Joyce D
FAU - Lisanti, Michael P
AU  - Lisanti MP
FAU - Albanese, Christopher
AU  - Albanese C
FAU - Pestell, Richard G
AU  - Pestell RG
LA  - eng
GR  - R01 CA075503/CA/NCI NIH HHS/United States
GR  - P30CA56036/CA/NCI NIH HHS/United States
GR  - R01 CA120876/CA/NCI NIH HHS/United States
GR  - R01CA75503/CA/NCI NIH HHS/United States
GR  - R01CA120876/CA/NCI NIH HHS/United States
GR  - R01 CA070896/CA/NCI NIH HHS/United States
GR  - R01CA107382/CA/NCI NIH HHS/United States
GR  - R01CA70896/CA/NCI NIH HHS/United States
GR  - R01 CA107382/CA/NCI NIH HHS/United States
GR  - R01CA86072/CA/NCI NIH HHS/United States
GR  - R01 CA070896-07A1/CA/NCI NIH HHS/United States
GR  - R01 CA086072/CA/NCI NIH HHS/United States
GR  - R01 CA107382-06/CA/NCI NIH HHS/United States
GR  - R01 CA075503-02/CA/NCI NIH HHS/United States
GR  - P30 CA056036/CA/NCI NIH HHS/United States
GR  - R01 CA086072-01A2/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 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Reactive Oxygen Species)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - Cell Growth Processes/physiology
MH  - Cell Transformation, Neoplastic/genetics/metabolism/*pathology
MH  - Epithelial Cells/pathology
MH  - Epithelial-Mesenchymal Transition
MH  - Female
MH  - I-kappa B Proteins/biosynthesis/genetics
MH  - Mammary Neoplasms, Experimental/genetics/metabolism/*pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Neoplastic Stem Cells/metabolism/*pathology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptor, ErbB-2/biosynthesis
MH  - Transfection
PMC - PMC3010731
MID - NIHMS247137
EDAT- 2010/12/17 06:00
MHDA- 2011/01/21 06:00
PMCR- 2011/12/15
CRDT- 2010/12/17 06:00
PHST- 2010/12/17 06:00 [entrez]
PHST- 2010/12/17 06:00 [pubmed]
PHST- 2011/01/21 06:00 [medline]
PHST- 2011/12/15 00:00 [pmc-release]
AID - 70/24/10464 [pii]
AID - 10.1158/0008-5472.CAN-10-0732 [doi]
PST - ppublish
SO  - Cancer Res. 2010 Dec 15;70(24):10464-73. doi: 10.1158/0008-5472.CAN-10-0732.