Cytosolic phospholipase A2-α expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours
| Autor: | Nina S. McCarthy, Brian J. Harvey, Arnold D.K. Hill, Warren Thomas, Leonie S. Young, Francesco Caiazza |
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| Rok vydání: | 2010 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Antineoplastic Agents Hormonal EGFR Receptor expression Breast Neoplasms Biology Cohort Studies Cytosol breast cancer Breast cancer Epidermal growth factor Gene expression medicine Humans RNA Messenger Epidermal growth factor receptor phospholipase skin and connective tissue diseases Molecular Diagnostics Oligonucleotide Array Sequence Analysis Predictive marker Reverse Transcriptase Polymerase Chain Reaction Cancer Prognosis medicine.disease ErbB Receptors Phospholipases A2 Oncology Cancer research biology.protein Female Breast disease oestrogen |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A2α (cPLA2α) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA2α expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines. Methods: The importance of differential cPLA2α activity in clinical breast cancer was established by relating the expression of cPLA2α in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters. Results: High cPLA2α mRNA expression correlated with clinical parameters of poor prognosis, which are characteristic of highly invasive tumours of the HER2-positive and basal-like subtype, including low oestrogen receptor expression and high EGFR expression. High cPLA2α expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA2α expression was an independent predictive parameter of poor response to endocrine therapy in the first 5 years of follow-up. Conclusion: This study shows a role of cPLA2α in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker. |
| Databáze: | OpenAIRE |
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