Phosphorylation of Estrogen Receptor-α at Ser167 Is Indicative of Longer Disease-Free and Overall Survival in Breast Cancer Patients
| Autor: | Elena Kulinskaya, Jie Jiang, David Peston, R. Charles Coombes, Sami Shousha, Naveed Sarwar, Simak Ali |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
inorganic chemicals
MAPK/ERK pathway Cancer Research medicine.medical_specialty Time Factors MAP Kinase Signaling System Estrogen receptor Breast Neoplasms macromolecular substances Models Biological Ribosomal Protein S6 Kinases 90-kDa environment and public health Disease-Free Survival Breast cancer Cell surface receptor Cell Line Tumor Internal medicine Serine medicine Humans Phosphorylation Protein kinase A Protein kinase B Kinase business.industry Estrogen Receptor alpha Prognosis medicine.disease enzymes and coenzymes (carbohydrates) Treatment Outcome Endocrinology Receptors Estrogen Oncology Disease Progression bacteria business |
| Zdroj: | Clinical Cancer Research. 13:5769-5776 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-07-0822 |
| Popis: | Purpose: Ser167 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 Ser167 phosphorylation is important in the regulation of ER activity and have identified p90RSK and AKT as protein kinases that phosphorylate Ser167. The purpose of this study was to determine the importance of Ser167 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 Ser167 and for phosphorylated p44/p42 mitogen-activated protein kinase (MAPK), phosphorylated p90RSK, and phosphorylated AKT. Results: In ER-positive breast cancer patients, Ser167 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, Ser167 phosphorylation was strongly associated with phosphorylated p90RSK (P < 0.001), previously shown to phosphorylate Ser167 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 Ser167 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 Ser167 of ER predicts for likelihood of response of ER-positive breast cancer patients to endocrine therapies. |
| Databáze: | OpenAIRE |
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