J Mol Endocrinol 2005,
PMID: 16326831
Zhang, S; Li, X; Burghardt, R; Smith, R; Safe, S H
Insulin-like growth factor-I (IGF-I) is a mitogenic polypeptide that induces proliferation of MCF-7 breast cancer cells, and cotreatment with the phosphoinositide 3-kinase (PI3-K) inhibitor LY294002 and the antiestrogen ICI 182780 inhibits IGF-I-induced growth. The role of estrogen receptor alpha (ERalpha) in mediating responses induced by IGF-I was investigated in cells transfected with small inhibitory RNA for ERalpha (iERalpha). The results showed that IGF-I-dependent phosphorylation of Akt and mitogen-activated protein kinase, induction of G(1)-S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERalpha. Moreover, these same IGF-I-induced responses were also inhibited by the antiestrogen ICI 182780 and this was in contrast to a previous report suggesting that ICI 182780 did not affect IGF-I-dependent activation of PI3-K or induction of cyclin D1 expression. ICI 182780 exhibits antimitogenic activity and iERalpha inhibits G(1)-S-phase progression and proliferation of MCF-7 cells treated with IGF-I, suggesting that the effects of the antiestrogen are primarily related to downregulation of ERalpha.
Diseases/Pathways annotated by Medline MESH: Breast Neoplasms, MAP Kinase Signaling System
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Text Mining Data
mitogen activated protein kinase → ERalpha: "
The results showed that IGF-I dependent phosphorylation of Akt and
mitogen activated protein kinase , induction of G ( 1 ) -S-phase progression and enhanced expression of cyclin D1 and cyclin E were
dependent on
ERalpha
"
mitogen activated protein kinase → IGF-I: "
The results showed that IGF-I dependent phosphorylation of Akt and mitogen activated protein kinase , induction of G ( 1 ) -S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERalpha
"
Akt → ERalpha: "
The results showed that IGF-I dependent phosphorylation of Akt and mitogen activated protein kinase, induction of G ( 1 ) -S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERalpha
"
Akt → IGF-I: "
The results showed that IGF-I dependent phosphorylation of Akt and mitogen activated protein kinase, induction of G ( 1 ) -S-phase progression and enhanced expression of cyclin D1 and cyclin E were dependent on ERalpha
"
cyclin D1 → IGF-I: "
Moreover, these same IGF-I induced responses were also inhibited by the antiestrogen ICI 182780 and this was in contrast to a previous report suggesting that ICI 182780 did not affect IGF-I dependent activation of PI3-K or induction of cyclin D1 expression
"
PI3-K → IGF-I: "
Moreover, these same IGF-I induced responses were also inhibited by the antiestrogen ICI 182780 and this was in contrast to a previous report suggesting that ICI 182780 did not affect IGF-I dependent activation of PI3-K or induction of cyclin D1 expression
"
Manually curated Databases
No curated data.