PMID- 12960057
OWN - NLM
STAT- MEDLINE
DCOM- 20031203
LR  - 20181130
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 144
IP  - 11
DP  - 2003 Nov
TI  - Growth factor-specific regulation of insulin receptor substrate-1 expression in 
      MCF-7 breast carcinoma cells: effects on the insulin-like growth factor signaling 
      pathway.
PG  - 4811-9
AB  - IGFs are potent mitogens that play a crucial role in cell proliferation and/or 
      differentiation and tumorigenesis. Insulin receptor substrate-1 (IRS-1) is a key 
      protein in the IGF signaling pathway in the estrogen-dependent MCF-7 breast 
      carcinoma cell line. In this study, three growth factors [fibroblast growth 
      factor (FGF), epidermal growth factor (EGF), and platelet-derived growth factor 
      (PDGF)] were tested for their ability to modulate IRS-1 protein expression and 
      the IGF-I signaling pathway. FGF and, to a lesser extent, EGF were found to 
      increase IRS-1 protein, whereas PDGF had no effect. This indicates that growth 
      factors can specifically modulate IRS-1 protein content. The increases provoked 
      by EGF and FGF were dependent on the MAPK signaling pathway but independent of 
      phosphatidylinositol 3-kinase (PI 3-kinase) signaling and required de novo 
      protein synthesis. We noted that the kinetics of MAPK activation was continuous 
      in response to FGF but transient in response to EGF. In addition, transfection of 
      cells with a constitutively active form of MAPK kinase, which results in 
      continuous MAPK activity, increased IRS-1 expression. Taken together, these 
      results suggest that stimulation of IRS-1 expression was therefore stronger when 
      MAPK activity was sustained. Pretreatment of cells with EGF, FGF, or PDGF for 24 
      h reduced IGF-I-induced tyrosine phosphorylation per molecule of IRS-1. However, 
      IGF-I-induced PI 3-kinase activity was decreased by 24 h of pretreatment with EGF 
      or PDGF but not with FGF. Our results therefore demonstrate that different growth 
      factors are capable of specifically modulating the IGF-I signaling via IRS-1. 
      They further suggest that the FGF-induced increase in IRS-1 counterbalances the 
      inhibition of IRS-1 tyrosine phosphorylation to allow normal stimulation of 
      IGF-I-induced PI 3-kinase activity.
FAU - Lassarre, Claudine
AU  - Lassarre C
AD  - Institut National de la Sante et de la Recherche Medicale, Unite 515, Hopital 
      Saint-Antoine, Paris, France.
FAU - Ricort, Jean-Marc
AU  - Ricort JM
LA  - eng
SI  - GENBANK/AF329730
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030724
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (IRS1 protein, human)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Phosphoproteins)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Proto-Oncogene Proteins c-sis)
RN  - 0 (Recombinant Proteins)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - 112603-35-7 (insulin-like growth factor 1, des-(1-3)-)
RN  - 1B56C968OA (Becaplermin)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (MAP2K2 protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 2)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
SB  - IM
MH  - Amino Acid Sequence/genetics
MH  - Base Sequence/genetics
MH  - Becaplermin
MH  - Breast Neoplasms/*metabolism/pathology
MH  - Cell Line, Tumor
MH  - Enzyme Inhibitors/pharmacology
MH  - Epidermal Growth Factor/*pharmacology
MH  - Female
MH  - Fibroblast Growth Factor 2/*pharmacology
MH  - Humans
MH  - Insulin Receptor Substrate Proteins
MH  - Insulin-Like Growth Factor I/metabolism/pharmacology
MH  - MAP Kinase Kinase 2
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinase Kinases/pharmacology
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors
MH  - Molecular Sequence Data
MH  - Peptide Fragments/pharmacology
MH  - Phosphoproteins/*metabolism
MH  - Platelet-Derived Growth Factor/*pharmacology
MH  - Protein-Tyrosine Kinases/pharmacology
MH  - Proto-Oncogene Proteins c-sis
MH  - Recombinant Proteins/pharmacology
MH  - Signal Transduction
EDAT- 2003/09/10 05:00
MHDA- 2003/12/04 05:00
CRDT- 2003/09/10 05:00
PHST- 2003/09/10 05:00 [pubmed]
PHST- 2003/12/04 05:00 [medline]
PHST- 2003/09/10 05:00 [entrez]
AID - en.2002-0205 [pii]
AID - 10.1210/en.2002-0205 [doi]
PST - ppublish
SO  - Endocrinology. 2003 Nov;144(11):4811-9. doi: 10.1210/en.2002-0205. Epub 2003 Jul 
      24.