PMID- 14997047
OWN - NLM
STAT- MEDLINE
DCOM- 20040513
LR  - 20190906
IS  - 0167-6806 (Print)
IS  - 0167-6806 (Linking)
VI  - 83
IP  - 2
DP  - 2004 Jan
TI  - Motility response to insulin-like growth factor-I (IGF-I) in MCF-7 cells is 
      associated with IRS-2 activation and integrin expression.
PG  - 161-70
AB  - In MCF-7L cells, insulin-like growth factor-I (IGF-I) stimulates activation of 
      insulin receptor substrate-1 (IRS-1) and enhances cell proliferation. While 
      others have shown that IGF-I enhances cell motility in MCF-7 cells, we have not 
      been able to demonstrate this. To determine if the source of MCF-7 cells account 
      for these reported differences, we examined the MCF-7 cells available from the 
      American Type Culture Collection (MCF-7/ATCC) and compared them to the MCF-7L 
      cells maintained in our laboratory. Both MCF-7L and MCF-7/ATCC grew in response 
      to 5 nM IGF-I and 1 nM estradiol. However, only MCF-7/ATCC demonstrated IGF-I 
      stimulated motility. Immunoprecipitation of IRS substrates followed by 
      anti-phosphotyrosine blotting demonstrated that both IRS-1 and IRS-2 were 
      activated by IGF-I in these cells. However, MCF-7/ATCC cells had greater 
      phosphorylation of IRS-2 compared to MCF-7L. Immunoblots showed that levels of 
      IRS-1 and IRS-2 were comparable between cell lines. We have previously shown that 
      fibronectin-binding integrins are necessary for IGF-stimulated motility. Similar 
      levels of beta1 integrin were detected in both strains of MCF-7. However, low 
      levels of alpha5 and alpha3 were detected in MCF-7L cells whereas high levels of 
      alpha3 and alpha5 integrin were expressed in MCF-7/ATCC cells. Inhibition of 
      integrin function by a blocking antibody or inhibitory peptide diminished 
      IGF-mediated motility in MCF-7/ATCC. In MCF-7/ATCC cells, IGF-I stimulation was 
      associated with a movement of IRS-2 to the leading edge of filopodia. Thus, 
      patterns of integrin expression among breast cancer cell lines may partially 
      explain the different motility behavior of cells in response to IGF-I. IRS-2 
      activation and integrin occupancy are both required for IGF-stimulated motility.
FAU - Zhang, Xihong
AU  - Zhang X
AD  - Department of Medicine, University of Minnesota Cancer Center, Minneapolis, MN 
      55455, USA.
FAU - Kamaraju, Sailaja
AU  - Kamaraju S
FAU - Hakuno, Fumihiko
AU  - Hakuno F
FAU - Kabuta, Tomohiro
AU  - Kabuta T
FAU - Takahashi, Shin-Ichiro
AU  - Takahashi S
FAU - Sachdev, Deepali
AU  - Sachdev D
FAU - Yee, Douglas
AU  - Yee D
LA  - eng
GR  - P30 CA77398/CA/NCI NIH HHS/United States
GR  - R01 CA74285/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Breast Cancer Res Treat
JT  - Breast cancer research and treatment
JID - 8111104
RN  - 0 (IRS2 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Integrins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Phosphoproteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Breast Neoplasms/*pathology
MH  - Cell Line, Tumor/drug effects
MH  - Cell Movement/*drug effects
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoblotting
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Integrins/metabolism
MH  - Intracellular Signaling Peptides and Proteins
MH  - Phosphoproteins/metabolism
EDAT- 2004/03/05 05:00
MHDA- 2004/05/14 05:00
CRDT- 2004/03/05 05:00
PHST- 2004/03/05 05:00 [pubmed]
PHST- 2004/05/14 05:00 [medline]
PHST- 2004/03/05 05:00 [entrez]
AID - 5254055 [pii]
AID - 10.1023/b:brea.0000010709.31256.c6 [doi]
PST - ppublish
SO  - Breast Cancer Res Treat. 2004 Jan;83(2):161-70. doi: 
      10.1023/b:brea.0000010709.31256.c6.