PMID- 11704861
OWN - NLM
STAT- MEDLINE
DCOM- 20011213
LR  - 20091119
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 20
IP  - 50
DP  - 2001 Nov 1
TI  - Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) 
      in metastatic variants of human breast cancer cell lines.
PG  - 7318-25
AB  - Insulin-like growth factors (IGFs) regulate breast cancer cell proliferation, 
      protect cells from apoptosis, and enhance metastasis. In this study, we examined 
      the IGF signaling pathway in two breast cancer cell lines selected for metastatic 
      behavior. LCC6 was selected for growth as an ascites tumor in athymic mice from 
      parental MDA-MB-435 cells (435P). The MDA-231BO cell line was derived from 
      osseous metastases that formed after intracardiac injection of the MDA-MB-231 
      cell line in athymic mice. Compared to the parental cell lines, IGF-I treatment 
      enhanced IRS-2 phosphorylation over IRS-1 in the metastatic variants. IGF-I 
      stimulated cell migration in the variant cells, but not in the parental cells. To 
      determine the role for IRS-2 in IGF-mediated motility, we transfected MDA-231BO 
      cells with an anti-sense IRS-2 construct. Transfected cells had decreased levels 
      of IRS-2 with diminished IGF-mediated motility and anchorage independent growth 
      when compared to control cells. However, adherence to fibronectin was enhanced in 
      the transfected cells compared to MDA-231BO cells. Our data show that breast 
      cancer cells selected for metastatic behavior in vivo have increased IRS-2 
      activation and signaling. In these cells, IGF-I enhances cell adhesion and 
      motility suggesting that IRS-2 may mediate these aspects of the malignant 
      phenotype.
FAU - Jackson, J G
AU  - Jackson JG
AD  - Department of Medicine, Division of Medical Oncology, University of Texas Health 
      Science Center at San Antonio, San Antonio, Texas, TX 78229, USA.
FAU - Zhang, X
AU  - Zhang X
FAU - Yoneda, T
AU  - Yoneda T
FAU - Yee, D
AU  - Yee D
LA  - eng
GR  - P30CA54174/CA/NCI NIH HHS/United States
GR  - R01CA74285/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (DNA, Antisense)
RN  - 0 (IRS2 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Irs2 protein, mouse)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Bone Neoplasms/pathology/secondary
MH  - Breast Neoplasms/*pathology
MH  - Cell Adhesion
MH  - Cell Division
MH  - Cell Movement/physiology
MH  - DNA, Antisense/genetics
MH  - Female
MH  - Humans
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Mice
MH  - Mice, Nude
MH  - Neoplasm Metastasis/*pathology
MH  - Neoplasm Proteins/genetics/*physiology
MH  - Phosphoproteins/genetics/*physiology
MH  - Phosphorylation/drug effects
MH  - Protein Processing, Post-Translational/drug effects
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Receptor, IGF Type 1/drug effects/physiology
MH  - Recombinant Fusion Proteins/physiology
MH  - Selection, Genetic
MH  - Signal Transduction
MH  - Transfection
MH  - Tumor Cells, Cultured/cytology
EDAT- 2001/11/13 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/13 10:00
PHST- 2001/01/17 00:00 [received]
PHST- 2001/08/08 00:00 [revised]
PHST- 2001/08/14 00:00 [accepted]
PHST- 2001/11/13 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/13 10:00 [entrez]
AID - 10.1038/sj.onc.1204920 [doi]
PST - ppublish
SO  - Oncogene. 2001 Nov 1;20(50):7318-25. doi: 10.1038/sj.onc.1204920.