IRS-1 expression and activation are not sufficient to activate downstream pathways and enable IGF-I growth response in estrogen receptor negative breast cancer cells.
Growth Horm IGF Res
; 9(5): 280-9, 1999 Oct.
Article
in En
| MEDLINE
| ID: mdl-10543935
ABSTRACT
IGF-responsive breast cancer cells activate insulin receptor substrate (IRS)-1 after IGF-I treatment. To determine if IRS-1 expression was sufficient to enable IGF-responsiveness, two IGF-I unresponsive breast cancer cell lines (MDA-MB-435A and MDA-MB-468) were transfected with IRS-1. While IGF-I caused tyrosine phosphorylation of IRS-1 in both transfected cell lines, increased MAP kinase activity was not seen. IGF-I treatment of 435A IRS-1 transfected cells resulted in minimal increased PI3 kinase activity associated with IRS-1, while IRS-2/PI3 kinase was greatly reduced. In MDA-MB-468 IRS-1 transfected cells, IGF-I caused increased IRS-1 associated PI3 kinase activity compared to parental cells, but at levels far below those observed in IGF-responsive MCF-7 cells. The transfected cells were also not responsive to IGF-I in monolayer growth. Thus, IRS-1 expression and activation alone are insufficient to mediate a proliferative response to IGF-I in breast cancer cells, and it is likely that maximal activation of downstream signaling pathways must also occur.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phosphoproteins
/
Breast Neoplasms
/
Insulin-Like Growth Factor I
/
Receptors, Estrogen
/
Gene Expression Regulation, Neoplastic
Limits:
Animals
/
Humans
Language:
En
Journal:
Growth Horm IGF Res
Journal subject:
ENDOCRINOLOGIA
Year:
1999
Document type:
Article
Affiliation country:
United States