Linked Life Data

16707456

Source:http://linkedlifedata.com/resource/pubmed/id/16707456

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2006-5-18
pubmed:abstractText
The epidermal growth factor (EGF) and insulin-like growth factor (IGF) signaling pathways are critically involved in cancer development and progression. However, how these two signals cross-talk with each other to regulate cancer cell growth is not clearly understood. In this study, we found that EGF remarkably induced expression of major IGF signaling components, insulin receptor substrate (IRS)-1 and IRS-2, an effect that could be blocked by EGF receptor (EGFR) tyrosine kinase inhibitors. Although both extracellular signal-regulated kinase and c-Jun NH(2)-terminal kinase (JNK) signaling pathways were involved in the EGF up-regulation of IRS-1, the IRS-2 induction by EGF was specifically mediated by JNK signaling. Consistent with this, EGF increased IRS-2 promoter activity, which was associated with recruitment of activator protein-1 (AP-1) transcription factors and was inhibited by blocking AP-1 activity. Moreover, EGF treatment enhanced IGF-I and integrin engagement-elicited tyrosine phosphorylation of IRS and their downstream signaling, such as binding to phosphatidylinositol 3'-kinase regulatory subunit p85. Finally, repressing the induction of IRS-2 levels abolished the EGF enhancement of cell motility, suggesting that increased IRS-2 is essential for the EGF regulation of breast cancer cell migration. Taken together, our results reveal a novel mechanism of cross-talk between the EGF and IGF signaling pathways, which could have implications in therapeutic applications of targeting EGFR in tumors. Because AP-1 activity is involved in breast cancer progression, our work may also suggest IRS-2 as a useful marker for aggressive breast cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5304-13
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Epidermal growth factor induces insulin receptor substrate-2 in breast cancer cells via c-Jun NH(2)-terminal kinase/activator protein-1 signaling to regulate cell migration.
pubmed:affiliation
Breast Center, Departments of Medicine and Molecular and Cellular Biology, Baylor College of Medicine and Methodist Hospital, Houston, Texas 77030, USA. cui@breastcenter.tmc.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural