AGR2, a novel metastasis inducing protein with an effect on breast cancer patient survival

DL Barraclough¹, H Innes², S Taylor³, MPA Davies², A Platt-Higgins³, DR Sibson², PS Rudland¹^,3 and R Barraclough³

¹Cancer Tissue Bank Research Centre, University of Liverpool, Liverpool, UK

²Clatterbridge Cancer Research Trust, JK Douglas Laboratories, Clatterbridge Hospital, Bebington, UK

³School of Biological Sciences, University of Liverpool, Liverpool, UK

from Breast cancer research: the past and the future
London, UK. 1 November 2006

Breast Cancer Research 2006, 8(Suppl 2):P15doi:10.1186/bcr1570

Published:

1 November 2006

Background

In order to provide potential diagnostic markers and to identify potential targets for breast cancer therapy, gene products that are differentially expressed between benign and malignant cells have been isolated and identified by a combination of PCR-selected suppression subtractive libraries [1,2] and inhouse cDNA microarrays, screened using mRNAs from human breast cancer specimens. A number of the cDNAs were differentially expressed by greater than twofold, including the one for AGR2, the secreted human homologue of a Xenopus developmental protein.

Methods and results

In an in vivo model system of metastasis, AGR2 induced metastases compared with no metastases in the control groups [3]. In immunocytochemistry with an inhouse affinity-purified AGR2 antiserum [3], the presence of AGR2 protein in tumour specimens was statistically significantly associated with malignancy, with oestrogen receptor (ER) alpha-positive carcinomas, with low histological grade and with reduced patient survival over a 10-year period of follow-up of a group of ER-positive cases [4].

Conclusion

Our results demonstrate that AGR2 is causatively involved in metastasis and associated with poor outcome in patients with breast cancer, indicating that AGR2 might be a valuable new potential diagnostic marker and possible target for breast cancer therapy. Further studies are essential to understand the mechanism of AGR2-induced metastasis.

Acknowledgements

The authors thank Clatterbridge Cancer Research Trust, The Cancer and Polio Research Fund Ltd and the Higher Education Funding Council for financial support.

References

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Innes HE, Liu D, Barraclough R, Davies MPA, O'Neill PA, Platt-Higgins A, de Silva Rudland S, Sibson DR, Rudland PS: Significance of the metastasis-inducing protein AGR2 for outcome in hormonally-treated breast cancer patients.
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This article is part of the supplement: Breast cancer research: the past and the future