Increased Level of Phosphorylated ShcA Measured by Chemiluminescence-Linked Immunoassay Is a Predictor of Good Prognosis in Primary Breast Cancer Expressing Low Levels of Estrogen Receptor
| Autor: | Urs Eppenberger, Serenella Eppenberger-Castori, Jonas Cicenas, Willy Küng |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
medicine.medical_specialty kinase ShcA Estrogen receptor lcsh:RC254-282 Article Receptor tyrosine kinase breast cancer Growth factor receptor Internal medicine medicine immunoassay Tyrosine biology phosphorylation Kinase business.industry lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Endocrinology Oncology biology.protein Cancer research biomarker Phosphorylation GRB2 Signal transduction business estrogen receptor |
| Zdroj: | Cancers Cancers, Vol 2, Iss 1, Pp 153-164 (2010) Volume 2 Issue 1 Pages 153-164 |
| ISSN: | 2072-6694 |
| DOI: | 10.3390/cancers2010153 |
| Popis: | The SH2 domain-containing adaptor protein ShcA is a proto-oncogene involved in growth factor receptor signaling. The role of phosphorylated ShcA is to link receptor tyrosine kinases with the SH2-containing adaptor protein Grb2, thus facilitating signal transduction from receptor tyrosine kinases to Ras, leading to MAPK activation. The present study was designed to investigate the prognostic significance of phosphorylated ShcA in primary breast cancer and its association in the interactions between the ER and ErbB2 pathways. Using a two-site chemiluminescence-linked immunosorbent assay, we detected the quantitative expression levels of total tyrosine- and threonine-phosphorylated ShcA in cytosol fractions obtained from fresh frozen tissue samples of 153 selected primary breast cancer patients. ShcA phosphorylation was not associated with nodal status, estrogen receptor (ER) status or grading. High levels of both tyrosine (pYShcA) and serine (pSShcA) phosphorylated ShcA correlated with good prognosis (p < 0.01), with respect to both disease-free (DFS) and overall survival (OS). In addition, pShcA levels were found to correlate with threonine-phosphorylated ErbB2 and inversely with phosphorylated Akt (pAkt), as well as ErbB2 and ER expression levels. Our findings demonstrate that ShcA activation in primary breast cancer patients correlates with low levels of ER, and is associated with good prognosis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|