Phosphorylation of Estrogen Receptor-α at Ser167 Is Indicative of Longer Disease-Free and Overall Survival in Breast Cancer Patients
2007
Purpose: Ser 167 was first identified as a major phosphorylation site of the estrogen receptor -α (ER) positive in the MCF7 breast cancer cell line. Subsequent studies have shown that Ser 167 phosphorylation is important in the regulation of ER activity and have identified p90RSK and AKT as protein kinases that phosphorylate Ser 167 . The purpose of this study was to determine the importance of Ser 167 phosphorylation in breast cancer progression. Experimental Design: Immunohistochemical staining of primary breast cancer biopsies ( n = 290) was carried out using antibodies specific for ER phosphorylated at Ser 167 and for phosphorylated p44/p42 mitogen-activated protein kinase (MAPK), phosphorylated p90RSK, and phosphorylated AKT. Results: In ER-positive breast cancer patients, Ser 167 phosphorylation was associated with low tumor grade ( P = 0.011), lymph node negativity ( P = 0.034), and relapse-free ( P = 0.006) and overall ( P = 0.023) survival. Further, Ser 167 phosphorylation was strongly associated with phosphorylated p90RSK ( P 167 in vitro , as well as being associated with phosphorylated MAPK ( P 167 phosphorylation nor were the activities of MAPK or p90RSK associated with HER2 status, suggesting that other cell surface receptors may be important in regulating these activities in breast cancer. Conclusions: These findings show that phosphorylation at Ser 167 of ER predicts for likelihood of response of ER-positive breast cancer patients to endocrine therapies.
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