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 -