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Breast Cancer Research
Published in: Breast Cancer Research 5/2005

Open Access 01-10-2005 | Research article

Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells

Authors: Xinqun Li, Yang Lu, Ke Liang, Bolin Liu, Zhen Fan

Published in: Breast Cancer Research | Issue 5/2005

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Abstract

Introduction

We have shown previously that overexpression of constitutively active Akt or activation of Akt caused by constitutively active Ras or human epidermal growth factor receptor-2 (HER2) confers on breast cancer cells resistance to chemotherapy or radiotherapy. As an expanded study we here report differential responses in terms of phosphorylation and activation of Akt as a result of treatment with doxorubicin in a panel of breast cancer cell lines.

Methods

The levels of Akt phosphorylation and activity were measured by Western blot analysis with an anti-Ser473-phosphorylated Akt antibody and by in vitro Akt kinase assay using glycogen synthase kinase-3 as a substrate.

Results

Within 24 hours after exposure to doxorubicin, MCF7, MDA468 and T47D cells showed a drug-dose-dependent increase in the levels of phosphorylated Akt; in contrast, SKBR3 and MDA231 cells showed a decrease in the levels of phosphorylated Akt, and minimal or no changes were detected in MDA361, MDA157 and BT474 cells. The doxorubicin-induced Akt phosphorylation was correlated with increased kinase activity and was dependent on phosphoinositide 3-kinase (PI3-K). An increased baseline level of Akt was also found in MCF7 cells treated with ionizing radiation. The cellular responses to doxorubicin-induced Akt phosphorylation were potentiated after the expression of Akt upstream activators including HER2, HER3 and focal adhesion kinase.

Conclusion

Taken together with our recent published results showing that constitutive Akt mediates resistance to chemotherapy or radiotherapy, our present data suggest that the doxorubicin-induced phosphorylation and activation of Akt might reflect a cellular defensive mechanism of cancer cells to overcome doxorubicin-induced cytotoxic effects, which further supports the current efforts of targeting PI3-K/Akt for enhancing the therapeutic responses of breast cancer cells to chemotherapy and radiotherapy.
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Metadata
Title
Differential responses to doxorubicin-induced phosphorylation and activation of Akt in human breast cancer cells
Authors
Xinqun Li
Yang Lu
Ke Liang
Bolin Liu
Zhen Fan
Publication date
01-10-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1259

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