Details

Autor(en) / Beteiligte

• JIE JIANG
• SARWAR, Naveed
• PESTON, David
• KULINSKAYA, Elena
• SHOUSHA, Sami
• COOMBES, R. Charles
• ALI, Simak

Titel

Phosphorylation of Estrogen Receptor-α at Ser167 Is Indicative of Longer Disease-Free and Overall Survival in Breast Cancer Patients

Ist Teil von

• Clinical cancer research, 2007-10, Vol.13 (19), p.5769-5776

Ort / Verlag

Philadelphia, PA: American Association for Cancer Research

Erscheinungsjahr

2007

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 < 0.001), previously shown to phosphorylate Ser 167 in vitro , as well as being associated with phosphorylated MAPK ( P < 0.0005). The activities of both kinases also seemed to be indicative of better prognosis. There was, however, no association between HER2 positivity and Ser 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.