Document Type

Article

Publication Date

1-18-2011

Keywords

Antineoplastic Agents, Hormonal, Breast Neoplasms, Cohort Studies, Cytosol, Female, Humans, Oligonucleotide Array Sequence Analysis, Phospholipases A2, Prognosis, RNA, Messenger, Receptor, Epidermal Growth Factor, Reverse Transcriptase Polymerase Chain Reaction

Comments

This article is also available at http://www.nature.com

Abstract

BACKGROUND: The eicosanoid signalling pathway promotes the progression of malignancies through the production of proliferative prostaglandins (PGs). Cytosolic phospholipase A(2)α (cPLA(2)α) activity provides the substrate for cyclooxygenase-dependent PG release, and we have previously found that cPLA(2)α expression correlated with EGFR/HER2 over-expression in a small number of breast cancer cell lines.

METHODS: The importance of differential cPLA(2)α activity in clinical breast cancer was established by relating the expression of cPLA(2)α in tissue samples from breast cancer patients, and two microarray-based gene expression datasets to different clinicopathological and therapeutic parameters.

RESULTS: High cPLA(2)α 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 cPLA(2)α expression decreased overall survival in patients with luminal cancers, and correlated with a reduced effect of tamoxifen treatment. The cPLA(2)α 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 cPLA(2)α in luminal breast cancer progression, in which the enzyme could represent a novel therapeutic target and a predictive marker.

Disciplines

Medical Molecular Biology | Medical Sciences

Citation

Caiazza F, McCarthy NS, Young L, Hill AD, Harvey BJ, Thomas W. Cytosolic phospholipase A2-α expression in breast cancer is associated with EGFR expression and correlates with an adverse prognosis in luminal tumours. British Journal of Cancer. 2011;104(2):338-44.

PubMed ID

21119660

DOI Link

10.1038/sj.bjc.6606025