Document Detail


Activation of a nuclear factor kappaB/interleukin-1 positive feedback loop by amphiregulin in human breast cancer cells.
MedLine Citation:
PMID:  17670913     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have recently shown that an amphiregulin-mediated autocrine loop is responsible for growth factor-independent proliferation, motility, and invasive capacity of some aggressive breast cancer cells, such as the SUM149 breast cancer cell line. In the present study, we investigated the mechanisms by which amphiregulin activation of the epidermal growth factor receptor (EGFR) regulates these altered phenotypes. Bioinformatic analysis of gene expression networks regulated by amphiregulin implicated interleukin-1alpha (IL-1alpha) and IL-1beta as key mediators of amphiregulin's biological effects. The bioinformatic data were validated in experiments which showed that amphiregulin, but not epidermal growth factor, results in transcriptional up-regulation of IL-1alpha and IL-1beta. Both IL-1alpha and IL-1beta are synthesized and secreted by SUM149 breast cancer cells, as well as MCF10A cells engineered to express amphiregulin or MCF10A cells cultured in the presence of amphiregulin. Furthermore, EGFR, activated by amphiregulin but not epidermal growth factor, results in the prompt activation of the transcription factor nuclear factor-kappaB (NF-kappaB), which is required for transcriptional activation of IL-1. Once synthesized and secreted from the cells, IL-1 further activates NF-kappaB, and inhibition of IL-1 with the IL-1 receptor antagonist results in loss of NF-kappaB DNA binding activity and inhibition of cell proliferation. However, SUM149 cells can proliferate in the presence of IL-1 when EGFR activity is inhibited. Thus, in aggressive breast cancer cells, such as the SUM149 cells, or in normal human mammary epithelial cells growing in the presence of amphiregulin, EGFR signaling is integrated with NF-kappaB activation and IL-1 synthesis, which cooperate to regulate the growth and invasive capacity of the cells.
Authors:
Katie L Streicher; Nicole E Willmarth; Jose Garcia; Julie L Boerner; T Gregory Dewey; Stephen P Ethier
Related Documents :
16666933 - Auxin and ethylene regulation of petiole epinasty in two developmental mutants of tomat...
18317963 - Growth inhibition of insulin-like growth factor i receptor monoclonal antibody to human...
23788393 - Reactive oxygen species induce cell death via akt signaling in rat osteoblast-like cell...
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2007-08-01
Journal Detail:
Title:  Molecular cancer research : MCR     Volume:  5     ISSN:  1541-7786     ISO Abbreviation:  Mol. Cancer Res.     Publication Date:  2007 Aug 
Date Detail:
Created Date:  2007-08-16     Completed Date:  2007-10-16     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  101150042     Medline TA:  Mol Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  847-61     Citation Subset:  IM    
Affiliation:
Barbara Ann Karmanos Cancer Institute, Detroit, MI 48201, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Breast Neoplasms / genetics,  metabolism,  pathology*
Cell Line
Cell Proliferation
Epithelial Cells / cytology,  metabolism
Feedback, Physiological*
Female
Glycoproteins / pharmacology*
Humans
Intercellular Signaling Peptides and Proteins / pharmacology*
Interleukin-1 / metabolism*
NF-kappa B / genetics,  metabolism*
Neoplasm Invasiveness / genetics,  physiopathology
Receptor, Epidermal Growth Factor / metabolism
Signal Transduction
Transforming Growth Factor beta1 / metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
R01 CA100724-05/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/Interleukin-1; 0/NF-kappa B; 0/Transforming Growth Factor beta1; 117147-70-3/amphiregulin; EC 2.7.10.1/Receptor, Epidermal Growth Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Impact of smoking and preexisting illness on estimates of the fractions of deaths associated with un...
Next Document:  Synergistic antiangiogenic effects of stathmin inhibition and taxol exposure.