PMID- 16510574
OWN - NLM
STAT- MEDLINE
DCOM- 20060418
LR  - 20161124
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 66
IP  - 5
DP  - 2006 Mar 1
TI  - 7,12-dimethylbenz(a)anthracene treatment of a c-rel mouse mammary tumor cell line 
      induces epithelial to mesenchymal transition via activation of nuclear 
      factor-kappaB.
PG  - 2570-5
AB  - The aberrant expression of the nuclear factor-kappaB (NF-kappaB) c-Rel subunit 
      that occurs in many human breast cancers can play a causal role in tumorigenesis 
      as judged by findings with a mouse mammary tumor virus (MMTV)-c-rel transgenic 
      mouse model, in which 31.6% of mice developed one or more mammary tumors after a 
      long latency. Interestingly, none of the cell lines established from the mammary 
      tumors grew in soft agar. To begin to test the hypothesis that a prototypic 
      carcinogen insult can promote a more invasive, mesenchymal phenotype, a cell line 
      established from a MMTV-c-rel mammary tumor rel-3983 was treated in culture with 
      the polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA; 
      rel-3983D cells) or DMSO vehicle (rel-3983V cells). Rel-3983D cells displayed an 
      increased rate of proliferation, displayed growth to a higher cell density, and 
      acquired the ability to grow in soft agar and in Matrigel compared with the 
      parental rel-3983 or vehicle-treated rel-3983V cells. Consistent with a more 
      mesenchymal phenotype, rel-3983D cells showed loss of E-cadherin expression as 
      judged by immunofluorescence microscopy. Compared with control cells, rel-3983D 
      displayed increased NF-kappaB binding and higher levels of the NF-kappaB 
      transactivating subunits c-Rel, RelA, and RelB, which seemed functional as judged 
      by induction of c-Myc and vimentin, products of two NF-kappaB target genes. 
      Ectopic expression of a super repressor mutant of IkappaB-alpha reduced rel-3983D 
      cell growth and invasive morphology in Matrigel, confirming the role of NF-kappaB 
      in epithelial to mesenchymal transition (EMT). Thus, DMBA treatment of 
      c-Rel-transformed mammary tumor cells in culture is shown here for the first time 
      to result in EMT via activation of NF-kappaB. The aberrant c-Rel expression 
      present in most human breast cancers suggests that this mechanism may play an 
      important role in carcinogenesis.
FAU - Shin, Sangmin Ryan
AU  - Shin SR
AD  - Department of Biochemistry and Environmental Health, Boston University Medical 
      Campus, Massachusetts 02118, USA.
FAU - Sanchez-Velar, Nuria
AU  - Sanchez-Velar N
FAU - Sherr, David H
AU  - Sherr DH
FAU - Sonenshein, Gail E
AU  - Sonenshein GE
LA  - eng
GR  - P01 ES11624/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Cadherins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Nfkbia protein, mouse)
RN  - 0 (Proto-Oncogene Proteins c-rel)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
SB  - IM
MH  - 9,10-Dimethyl-1,2-benzanthracene/*pharmacology
MH  - Animals
MH  - Cadherins/biosynthesis
MH  - Carcinoma, Adenosquamous/chemically induced/genetics/metabolism/*pathology
MH  - Cell Adhesion/drug effects
MH  - Cell Growth Processes/drug effects
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic/*chemically induced/genetics/metabolism/pathology
MH  - Epithelial Cells/drug effects/metabolism/pathology
MH  - *Genes, rel
MH  - I-kappa B Proteins/biosynthesis/genetics
MH  - Mammary Neoplasms, Experimental/chemically induced/genetics/metabolism/*pathology
MH  - Mesoderm/drug effects/metabolism/pathology
MH  - Mice
MH  - Mice, Transgenic
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/biosynthesis/*metabolism
MH  - Proto-Oncogene Proteins c-rel/biosynthesis/genetics
EDAT- 2006/03/03 09:00
MHDA- 2006/04/19 09:00
CRDT- 2006/03/03 09:00
PHST- 2006/03/03 09:00 [pubmed]
PHST- 2006/04/19 09:00 [medline]
PHST- 2006/03/03 09:00 [entrez]
AID - 66/5/2570 [pii]
AID - 10.1158/0008-5472.CAN-05-3056 [doi]
PST - ppublish
SO  - Cancer Res. 2006 Mar 1;66(5):2570-5. doi: 10.1158/0008-5472.CAN-05-3056.