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Links between ERK phosphorylation status and response to breast cancer treatment

Svensson S et al. (2005) ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis. Oncogene 24: 4370–4379

Extracellular signal-regulated kinases (ERKs) are signaling proteins that are regulated by reversible phosphorylation. They are involved in many cellular processes, including differentiation, migration, proliferation and cell death. Studies have found increased expression and activity of ERKs in cancer tissue, and an association with relapse after treatment. To clarify the role played by ERK proteins 1 and 2 (ERK1/2) in the signaling cascade in breast cancer, Svensson et al. studied three cohorts of patients with various stages of breast cancer, comprising 886 patients who received a variety of treatments (cohort I), 248 postmenopausal patients randomized during an earlier trial to receive either no adjuvant treatment or treatment with tamoxifen (cohort II), and a reference group of 524 consecutively diagnosed patients (cohort III).

The authors determined the ERK-phosphorylation status of primary tumor tissue using immunohistochemistry and assessed its effect on the response to tamoxifen treatment and clinical outcome. Higher levels of ERK1/2 phosphorylation correlated with smaller tumor size in two cohorts, and with longer survival in 'untreated' patients from cohort II. Estrogen-receptor-positive tumors respond well to tamoxifen, but ERK1/2 phosphorylation abrogated the response. The authors determined a signaling cascade leading from vascular endothelial growth factor receptor 2 to ERK1/2 phosphorylation to phosphorylation of the gene-transcription factor Ets-2. ERK 1/2 phosphorylation status correlated significantly with Ets-2 phosphorylation, and phosphorylation of this transcription factor was inversely associated with tumor size. Information from this study could help to improve strategies for tamoxifen treatment and might be of value when determining prognosis.

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Ireland, R. Links between ERK phosphorylation status and response to breast cancer treatment. Nat Rev Clin Oncol 2, 484 (2005). https://doi.org/10.1038/ncponc0254

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