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Breast Cancer Research
Published in: Breast Cancer Research 5/2008

Open Access 01-10-2008 | Research article

Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients

Authors: Galatea Kallergi, Sofia Agelaki, Antonia Kalykaki, Christos Stournaras, Dimitris Mavroudis, Vassilis Georgoulias

Published in: Breast Cancer Research | Issue 5/2008

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Abstract

Introduction

The phosphoinositide-3 kinase (PI3K)/Akt pathway, operating downstream of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER)2, is implicated in cell migration and survival. EGFR and HER2 are expressed in circulating tumor cells, but the activation status of downstream signaling molecules has not yet been reported.

Methods

To investigate expression levels of EGFR, HER2, PI3K, and Akt in circulating tumor cells, we used peripheral blood mononuclear cells from 32 cytokeratin-19 mRNA-positive patients with early (n = 16) and metastatic (n = 16) breast cancer.
Peripheral blood mononuclear cell cytospins were double stained with cytokeratin antibody along with one of the following: EGFR, phospho-EGFR, HER2, phospho-PI3K, or phospho-Akt antibodies.

Results

EGFR and HER2 were expressed in circulating tumor cells of 38% and 50% patients with early and 44% and 63% patients with metastatic disease, respectively. Interestingly, phospho-PI3K and phospho-Akt expression levels were similar at 88% (14 out of 16) and 81% (13 out of 16), respectively, in circulating tumor cells of patients with early and metastatic disease. Phospho-EGFR was observed in circulating tumor cells of two (33%) early and six (86%) metastatic EGFR-positive patients. Immunomagnetic separation of peripheral blood mononuclear cells, using EpCAM antibody, and subsequent double-staining experiments of circulating tumor cells showed that EGFR was co-expressed with HER2, phospho-Akt and phospho-PI3K kinases, indicating activation of the corresponding survival signaling pathway.

Conclusions

Our findings demonstrate that circulating tumor cells express receptors and activated signaling kinases of the EGFR/HER2/PI3K/Akt pathway, which could be used as targets for their effective elimination.
Appendix
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Metadata
Title
Phosphorylated EGFR and PI3K/Akt signaling kinases are expressed in circulating tumor cells of breast cancer patients
Authors
Galatea Kallergi
Sofia Agelaki
Antonia Kalykaki
Christos Stournaras
Dimitris Mavroudis
Vassilis Georgoulias
Publication date
01-10-2008
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2008
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2149

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