A conditional feedback loop regulates Ras activity through EphA2.
Cancer Cell
; 8(2): 111-8, 2005 Aug.
Article
in En
| MEDLINE
| ID: mdl-16098464
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.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Down-Regulation
/
Ras Proteins
/
Receptor, EphA2
Limits:
Animals
/
Humans
Language:
En
Journal:
Cancer Cell
Journal subject:
NEOPLASIAS
Year:
2005
Type:
Article
Affiliation country:
United States