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

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.

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].

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.