PMID- 21302279
OWN - NLM
STAT- MEDLINE
DCOM- 20111013
LR  - 20211020
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 226
IP  - 10
DP  - 2011 Oct
TI  - Knock-down of amphiregulin inhibits cellular invasion in inflammatory breast 
      cancer.
PG  - 2691-701
LID - 10.1002/jcp.22620 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Wiley-Liss, Inc.
FAU - Baillo, Andrea
AU  - Baillo A
AD  - Department of Oncology, Wayne State University, Detroit, Michigan, USA.
FAU - Giroux, Craig
AU  - Giroux C
FAU - Ethier, Stephen P
AU  - Ethier SP
LA  - eng
GR  - R01 CA130933/CA/NCI NIH HHS/United States
GR  - T32 CA009531/CA/NCI NIH HHS/United States
GR  - T32 CA009531-23/CA/NCI NIH HHS/United States
GR  - T32 CAO9531-23/PHS HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Amphiregulin
MH  - Cell Line, Tumor
MH  - EGF Family of Proteins
MH  - ErbB Receptors/physiology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/*physiology
MH  - Gene Knockdown Techniques/methods
MH  - Glycoproteins/*antagonists & inhibitors/*genetics/physiology
MH  - Humans
MH  - Inflammatory Breast Neoplasms/*genetics/metabolism/*pathology
MH  - Intercellular Signaling Peptides and Proteins/*genetics/physiology
MH  - Neoplasm Invasiveness/pathology
MH  - Phenotype
MH  - RNA, Small Interfering/pharmacology
MH  - Signal Transduction/genetics/physiology
PMC - PMC3865809
MID - NIHMS275070
EDAT- 2011/02/09 06:00
MHDA- 2011/10/14 06:00
PMCR- 2013/12/17
CRDT- 2011/02/09 06:00
PHST- 2011/02/09 06:00 [entrez]
PHST- 2011/02/09 06:00 [pubmed]
PHST- 2011/10/14 06:00 [medline]
PHST- 2013/12/17 00:00 [pmc-release]
AID - 10.1002/jcp.22620 [doi]
PST - ppublish
SO  - J Cell Physiol. 2011 Oct;226(10):2691-701. doi: 10.1002/jcp.22620.