Abstract
The EphA2 receptor tyrosine kinase is frequently overexpressed in many cancers, including 40% of breast cancers. Here, we show that EphA2 is a direct transcriptional target of the Ras-Raf-MAPK pathway and that ligand-stimulated EphA2 attenuates the growth factor-induced activation of Ras. Thus, a negative feedback loop is created that regulates Ras activity. Interestingly, the expression of EphA2 and ephrin-A1 is mutually exclusive in a panel of 28 breast cancer cell lines. We show that the MAPK pathway inhibits ephrin-A1 expression, and the ligand expression inhibits EphA2 levels contributing to the receptor-ligand reciprocal expression pattern in these cell lines. Our results suggest that an escape from the negative effects of this interaction may be important in the development of cancer.
Original language | English (US) |
---|---|
Pages (from-to) | 111-118 |
Number of pages | 8 |
Journal | Cancer Cell |
Volume | 8 |
Issue number | 2 |
DOIs | |
State | Published - Aug 2005 |
Externally published | Yes |
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ASJC Scopus subject areas
- Cancer Research
- Cell Biology
- Oncology
Cite this
A conditional feedback loop regulates Ras activity through EphA2. / Macrae, Madhu; Neve, Richard M.; Rodriguez-Viciana, Pablo; Haqq, Christopher; Yeh, Jennifer; Chen, Chira; Gray, Joe; McCormick, Frank.
In: Cancer Cell, Vol. 8, No. 2, 08.2005, p. 111-118.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A conditional feedback loop regulates Ras activity through EphA2
AU - Macrae, Madhu
AU - Neve, Richard M.
AU - Rodriguez-Viciana, Pablo
AU - Haqq, Christopher
AU - Yeh, Jennifer
AU - Chen, Chira
AU - Gray, Joe
AU - McCormick, Frank
PY - 2005/8
Y1 - 2005/8
N2 - The EphA2 receptor tyrosine kinase is frequently overexpressed in many cancers, including 40% of breast cancers. Here, we show that EphA2 is a direct transcriptional target of the Ras-Raf-MAPK pathway and that ligand-stimulated EphA2 attenuates the growth factor-induced activation of Ras. Thus, a negative feedback loop is created that regulates Ras activity. Interestingly, the expression of EphA2 and ephrin-A1 is mutually exclusive in a panel of 28 breast cancer cell lines. We show that the MAPK pathway inhibits ephrin-A1 expression, and the ligand expression inhibits EphA2 levels contributing to the receptor-ligand reciprocal expression pattern in these cell lines. Our results suggest that an escape from the negative effects of this interaction may be important in the development of cancer.
AB - The EphA2 receptor tyrosine kinase is frequently overexpressed in many cancers, including 40% of breast cancers. Here, we show that EphA2 is a direct transcriptional target of the Ras-Raf-MAPK pathway and that ligand-stimulated EphA2 attenuates the growth factor-induced activation of Ras. Thus, a negative feedback loop is created that regulates Ras activity. Interestingly, the expression of EphA2 and ephrin-A1 is mutually exclusive in a panel of 28 breast cancer cell lines. We show that the MAPK pathway inhibits ephrin-A1 expression, and the ligand expression inhibits EphA2 levels contributing to the receptor-ligand reciprocal expression pattern in these cell lines. Our results suggest that an escape from the negative effects of this interaction may be important in the development of cancer.
UR - http://www.scopus.com/inward/record.url?scp=23644451946&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23644451946&partnerID=8YFLogxK
U2 - 10.1016/j.ccr.2005.07.005
DO - 10.1016/j.ccr.2005.07.005
M3 - Article
C2 - 16098464
AN - SCOPUS:23644451946
VL - 8
SP - 111
EP - 118
JO - Cancer Cell
JF - Cancer Cell
SN - 1535-6108
IS - 2
ER -