Document Detail


Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast cancer.
MedLine Citation:
PMID:  21302279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We have previously shown that SUM-149 human breast cancer cells require an amphiregulin (AREG) autocrine loop for cell proliferation. We also demonstrated that AREG can increase epidermal growth factor receptor (EGFR) stability and promote EGFR localization to the plasma membrane. In the present studies we successfully knocked-down AREG expression in SUM-149 cells by lentiviral infection of AREG shRNA. In the absence of AREG expression, SUM-149 cell growth was slowed, but not completely inhibited. Furthermore, cells infected with AREG shRNA constructs showed an increase in EGFR protein expression by Western blot. Immunofluorescence and confocal microscopy showed that following AREG knock-down, EGFR continued to localize to the cell surface. Soft agar assays demonstrated that AREG knock-down cells retain anchorage-independent growth capacity. Additionally mammosphere forming assays and Adefluor staining analysis showed that knock-down of AREG expression did not affect the expression of stem cell phenotypes. However, following AREG knock-down, SUM-149 cells demonstrated a dramatic decrease in their ability to invade a Matrigel matrix. Consistent with this observation, microarray analysis comparing cells infected with a non-silencing vector to the AREG knock-down cells, identified genes associated with the invasive phenotype such as RHOB and DKK1, and networks associated with cell motility such as integrin-linked kinase signaling, and focal adhesion kinase signaling. AREG was also found to modulate WNT and Notch signaling in these cells. Thus, AREG functions in regulating the invasive phenotype, and we propose that this regulation may be through altered signaling that occurs when AREG activates plasma membrane localized EGFR.
Authors:
Andrea Baillo; Craig Giroux; Stephen P Ethier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  226     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-07-27     Completed Date:  2011-10-13     Revised Date:  2014-09-24    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2691-701     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Wiley-Liss, Inc.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic / physiology*
Gene Knockdown Techniques / methods
Glycoproteins / antagonists & inhibitors*,  genetics*,  physiology
Humans
Inflammatory Breast Neoplasms / genetics*,  metabolism,  pathology*
Intercellular Signaling Peptides and Proteins / genetics*,  physiology
Neoplasm Invasiveness / pathology
Phenotype
RNA, Small Interfering / pharmacology
Receptor, Epidermal Growth Factor / physiology
Signal Transduction / genetics,  physiology
Grant Support
ID/Acronym/Agency:
R01 CA130933/CA/NCI NIH HHS; R01 CA130933/CA/NCI NIH HHS; T32 CA009531/CA/NCI NIH HHS; T32 CA009531-23/CA/NCI NIH HHS; T32 CAO9531-23//PHS HHS
Chemical
Reg. No./Substance:
0/Glycoproteins; 0/Intercellular Signaling Peptides and Proteins; 0/RNA, Small Interfering; 117147-70-3/amphiregulin; EC 2.7.10.1/Receptor, Epidermal Growth Factor
Comments/Corrections

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


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