Epidermal Growth Factor Receptor (EGFR)-mediated Positive Feedback of Protein-tyrosine Phosphatase epsilon (PTP epsilon) on ERK1/2 and AKT Protein Pathways Is Required for Survival of Human Breast Cancer Cells
Por:
C. NUNES-XAVIER, A. ELSON and R. PULIDO
Publicada:
27 ene 2012
Resumen:
Increased tyrosine phosphorylation has been correlated with human cancer, including breast cancer. In general, the activation of tyrosine kinases (TKs) can be antagonized by the action of protein-tyrosine phosphatases (PTPs). However, in some cases PTPs can potentiate the activation of TKs. In this study, we have investigated the functional role of PTP is an element of in human breast cancer cell lines. We found the up-regulation and activation of receptor PTP is an element of (RPTP is an element of) in MCF-7 cells and MDA-MB-231 upon PMA, FGF, and serum stimulation, which depended on EGFR and ERK1/2 activity. Diminishing the expression of PTP is an element of in human breast cancer cells abolished ERK1/2 and AKT activation, and decreased the viability and anchorage-independent growth of the cells. Conversely, stable MCF-7 cell lines expressing inducible high levels of ectopic PTP is an element of displayed higher activation of ERK1/2 and anchorage-independent growth. Our results demonstrate that expression of PTP is an element of is up-regulated and activated in breast cancer cell lines, through EGFR, by sustained activation of the ERK1/2 pathway, generating a positive feedback regulatory loop required for survival of human breast cancer cells.
Filiaciones:
C. NUNES-XAVIER:
Ctr Invest Principe Felipe, Valencia 46013, Spain
A. ELSON:
Weizmann Inst Sci, IL-76100 Rehovot, Israel
:
Ctr Invest Principe Felipe, Valencia 46013, Spain
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